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Campbell Chapter 12 - The Cell Cycle

Page 1:

  • Key Concepts 12.1, 12.2, and 12.3

  • Cell division is the ability of organisms to produce more of their own kind

  • Rudolf Virchow's concept of "Omnis cellula e cellula"

  • Cell division plays important roles in reproduction, development, and renewal/repair

  • The cell cycle and its phases

  • The distribution of chromosomes to daughter cells during cell division

Page 2:

  • Chapter 12: The Cell Cycle

  • The cell division process is part of the cell cycle

  • Passing identical genetic material to cellular offspring is a crucial function of cell division

  • Most cell division results in genetically identical daughter cells

  • DNA replication and distribution in cell division

  • Chromosomes and their structure

  • Characteristics of eukaryotic chromosomes

  • The number of chromosomes in different eukaryotic species

Page 3:

  • Mitosis is the division of genetic material in the nucleus

    • Followed immediately by cytokinesis, the division of the cytoplasm

    • Results in two cells that are genetically equivalent to the parent cell

  • From a fertilized egg, mitosis and cytokinesis produce somatic cells

    • Somatic cells have 23 pairs of chromosomes, one set inherited from each parent

  • Reproductive cells, or gametes, have half as many chromosomes as somatic cells

    • Human gametes have one set of 23 chromosomes

  • The number of chromosomes in somatic cells varies among species

Distribution of Chromosomes During Eukaryotic Cell Division:

  • When a cell is not dividing, each chromosome is in the form of a long, thin chromatin fiber

  • After DNA replication, the chromosomes condense as part of cell division

    • Chromosomes become densely coiled and folded, visible with a light microscope

  • Each duplicated chromosome consists of two sister chromatids

    • Sister chromatids are joined copies of the original chromosome

  • Sister chromatids are attached all along their lengths by protein complexes called cohesins

  • Each sister chromatid has a centromere, a region where it is attached most closely to its sister chromatid

  • Later in the cell division process, sister chromatids separate and move into two new nuclei

  • Once separated, sister chromatids are considered individual chromosomes

  • This step essentially doubles the number of chromosomes during cell division

Figure 12.4:

  • Shows a highly condensed, duplicated human chromosome

  • Chromosome duplication and condensation occur during cell division

  • Each duplicated chromosome consists of two sister chromatids connected by sister chromatid cohesion

  • Sister chromatids contain a copy of the DNA molecule

  • Molecular and mechanical processes separate sister chromatids into two chromosomes and distribute them to daughter cells

Figure 12.5:

  • Illustrates chromosome duplication and distribution during cell division

  • Asks how many chromatid arms the chromosome in Figure 2 has

  • Shows the point where one chromosome becomes two

BioFlix® Animation: Chromosome Duplication:

  • Provides an animation of chromosome duplication during cell division

Page 4:

  • The cell cycle consists of four phases: G1, S, G2, and M.

    • G1 is the growth phase where the cell continues to grow.

    • S is the synthesis phase where DNA replication occurs.

    • G2 is the phase where the cell completes preparations for cell division.

    • M is the phase where the cell divides.

  • The duration of each phase varies in different types of cells.

    • The M phase occupies less than 1 hour.

    • The S phase occupies 10-12 hours, about half the cycle.

    • The G1 and G2 phases together occupy the rest of the time.

  • Some cells in a multicellular organism divide infrequently or not at all and spend their time in G1 or G0 phase.

  • Mitosis is conventionally broken down into five stages: prophase, prometaphase, metaphase, anaphase, and telophase.

  • Cytokinesis completes the mitotic phase.

Page 4-5:

  • The mitotic spindle, made of microtubules, plays a crucial role in mitosis.

  • Meiosis is a variation of cell division that produces gametes with half the number of chromosomes as the parent cell.

  • Meiosis in humans occurs in special cells in the ovaries or testes.

  • Fertilization fuses two gametes together and restores the chromosome number.

  • Mitosis conserves the chromosome number in every somatic cell nucleus of the new individual.

  • The remainder of the chapter focuses on mitosis and the cell cycle in eukaryotes.

Page 5:

  • Mitosis is just one part of the cell cycle, which also includes interphase.

  • Interphase is a much longer stage that accounts for about 90% of the cell cycle.

  • Interphase can be divided into three phases: G1, S, and G2.

  • During interphase, the cell grows by producing proteins and cytoplasmic organelles.

  • Mitosis and cytokinesis make up the mitotic phase of the cell cycle.

  • Mitosis distributes the daughter chromosomes to daughter nuclei, while cytokinesis divides the cytoplasm to produce two daughter cells.

Page 5:

  • Prophase is the first stage of mitosis where chromatin fibers condense into discrete chromosomes.

  • The nucleoli disappear, and the mitotic spindle begins to form.

  • Prometaphase is the stage where the nuclear envelope fragments, and microtubules invade the nuclear area.

  • The chromosomes become even more condensed, and kinetochores form at the centromere of each chromatid.

  • Microtubules attach to the kinetochores and jerk the chromosomes back and forth.

  • Nonkinetochore microtubules interact with those from the opposite pole of the spindle, lengthening the cell.

Page 6:

Main ideas:

  • Metaphase: centrosomes at opposite poles, chromosomes at metaphase plate, kinetochores attached to microtubules

  • Anaphase: cohesin proteins cleaved, sister chromatids become independent chromosomes, chromosomes move towards opposite ends of the cell

  • Telophase and Cytokinesis: daughter nuclei form, nuclear envelopes arise, nucleoli reappear, chromosomes become less condensed, remaining spindle microtubules depolymerized, division of cytoplasm begins

Supporting details:

  • Metaphase:

    • Centrosomes at opposite poles of the cell

    • Chromosomes at the metaphase plate, with centromeres at the plate

    • Kinetochores of sister chromatids attached to kinetochore microtubules from opposite poles

  • Anaphase:

    • Shortest stage of mitosis

    • Cohesin proteins cleaved, allowing sister chromatids to separate

    • Daughter chromosomes move towards opposite ends of the cell as kinetochore microtubules shorten

    • Centromeres are pulled ahead of the arms, moving at a rate of about 1 µm/min

    • Cell elongates as nonkinetochore microtubules lengthen

    • By the end of anaphase, both ends of the cell have complete collections of chromosomes

  • Telophase and Cytokinesis:

    • Two daughter nuclei form in the cell

    • Nuclear envelopes form from fragments of the parent cell's nuclear envelope and other portions of the endomembrane system

    • Nucleoli reappear

    • Chromosomes become less condensed

    • Remaining spindle microtubules are depolymerized

    • Mitosis is complete, resulting in the division of one nucleus into two genetically identical nuclei

    • Cytokinesis begins, resulting in the division of the cytoplasm

    • In animal cells, cytokinesis involves the formation of a cleavage furrow

Page 7:

Main ideas:

  • Structure and function of the spindle during anaphase

  • Spindle microtubules elongate and shorten

  • Centrosomes and centrioles in animal cells

  • Kinetochore microtubules and movement of chromosomes

  • Metaphase plate and interaction of microtubules

Supporting details:

  • Structure and function of the spindle during anaphase:

    • Spindle correlates well with its function during anaphase

    • Anaphase begins when cohesins holding sister chromatids are cleaved by separase

    • Chromatids become individual chromosomes that move towards opposite ends of the cell

  • Spindle microtubules elongate and shorten:

    • Spindle microtubules elongate by incorporating more subunits of the protein tubulin

    • Spindle microtubules shorten by losing subunits

  • Centrosomes and centrioles in animal cells:

    • Spindle microtubules assemble at the centrosome, a subcellular region that organizes the cell's microtubules

    • Centrosome contains a pair of centrioles, but they are not essential for cell division

    • Centrioles are not present in plant cells, which still form mitotic spindles

  • Kinetochore microtubules and movement of chromosomes:

    • Each sister chromatid of a duplicated chromosome has a kinetochore

    • Kinetochore microtubules attach to kinetochores during prometaphase

    • Chromosomes move towards the pole from which the microtubules extend

    • Movement stops when microtubules from the opposite pole attach to the kinetochore on the other chromatid

    • Chromosome moves back and forth before settling midway between the two ends of the cell

  • Metaphase plate and interaction of microtubules:

    • Metaphase plate is a plane midway between the spindle's two poles

    • Metaphase plate is an imaginary plate, not an actual cellular structure

    • Microtubules that do not attach to kinetochores elongate and overlap with other nonkinetochore microtubules from the opposite pole

    • Asters, radial arrays of short microtubules, extend from each centrosome

Page 8: The Cell Cycle

Kinetochore microtubules function in poleward movement of chromosomes

  • Two mechanisms involving motor proteins are at play

  • Motor proteins on kinetochores "walk" chromosomes along microtubules

  • Microtubules depolymerize at kinetochore ends after motor proteins pass

  • Chromosomes are also "reeled in" by motor proteins at spindle poles

  • Microtubules depolymerize after passing by motor proteins at poles

  • Both mechanisms are used, with varying contributions among cell types

Nonkinetochore microtubules elongate the whole cell during anaphase

  • Responsible for elongating the cell during anaphase

  • Nonkinetochore microtubules from opposite poles overlap during metaphase

  • Motor proteins attached to microtubules walk them away from each other

  • Microtubules push apart, elongating the cell

  • Microtubules lengthen by the addition of tubulin subunits to their ends

  • Duplicate groups of chromosomes arrive at opposite ends of the cell

Cytokinesis in animal cells occurs through cleavage

  • Cleavage furrow appears near the old metaphase plate

  • Contractile ring of actin microfilaments and myosin molecules forms

  • Actin microfilaments interact with myosin, causing the ring to contract

  • Cleavage furrow deepens until the parent cell is pinched in two

  • Produces two completely separated cells with their own nucleus and cytosol

Cytokinesis in plant cells involves the formation of a cell plate

  • No cleavage furrow

  • Vesicles from the Golgi apparatus move to the middle of the cell

  • Vesicles coalesce to form a cell plate

  • Cell wall materials are deposited along the cell plate

  • Eventually, the cell plate becomes the new cell wall

Page 9: Inquiry - At which end do kinetochore microtubules shorten during anaphase?

Experiment by Gary Borisy and colleagues

  • Labeled microtubules of a pig kidney cell in early anaphase with a yellow fluorescent dye

  • Marked a region of the kinetochore microtubules between one spindle pole and the chromosomes

  • Used a laser to eliminate fluorescence from the marked region

  • Monitored changes in microtubule length on either side of the mark

Results of the experiment

  • Microtubule segments on the kinetochore side of the mark shortened

  • Microtubule segments on the spindle pole side stayed the same length

Conclusion of the experiment

  • Chromosome movement is correlated with kinetochore microtubules shortening at their kinetochore ends

  • Microtubules depolymerize at kinetochore ends, releasing tubulin subunits

  • Supports the hypothesis that chromosomes are walked along microtubules during anaphase

Page 9: Animation - Microtubule Depolymerization

  • Animation demonstrating the process of microtubule depolymerization during anaphase

Page 9:

  • Cytokinesis in animal and plant cells

    • Animal cells: cleavage of the cell through a cleavage furrow

    • Plant cells: formation of a cell plate

      • Vesicles carrying cell wall material collect inside the cell plate

      • Cell plate enlarges and fuses with the plasma membrane

      • Two daughter cells are formed, each with its own plasma membrane

      • A new cell wall forms between the daughter cells

  • Binary fission in bacteria

    • Bacteria and archaea can undergo binary fission

    • Binary fission refers to the process of cell division in half

    • Bacterial binary fission does not involve mitosis

    • Bacterial chromosomes are circular DNA molecules

    • Replication of bacterial chromosomes and distribution to daughter cells is a challenge

    • DNA replication starts at the origin of replication

    • One origin moves towards the opposite end of the cell as replication continues

    • Cell elongates during replication

    • When replication is complete and the cell has doubled in size, the plasma membrane pinches inward, dividing the cell into two daughter cells

    • Bacterial chromosomes move similar to the movement of centromeres in eukaryotic chromosomes during anaphase of mitosis

    • Proteins play important roles in bacterial chromosome movement and cell division

Page 10:

  • The evolution of mitosis

    • Mitosis may have evolved from simpler prokaryotic mechanisms of cell reproduction

    • Proteins involved in bacterial binary fission are related to eukaryotic proteins involved in mitosis

    • Variations of cell division exist in different organisms

    • Unicellular eukaryotes such as dinoflagellates, diatoms, and some yeasts have nuclear division processes that resemble ancestral mechanisms

    • Nuclear envelope remains intact during these types of nuclear division

    • Hypothesis uses currently existing species as examples and ignores potential intermediate mechanisms used by extinct species

Page 11:

  • Question 1: How many chromosomes are shown in the illustration in Figure 12.8? Are they duplicated? How many chromatids are shown?

    • The illustration in Figure 12.8 shows 6 chromosomes.

    • The chromosomes are duplicated, as each chromosome consists of two identical chromatids.

  • Question 2: Compare cytokinesis in animal cells and plant cells.

    • In animal cells, cytokinesis occurs through the formation of a cleavage furrow, which pinches the cell membrane inward until the cell is divided into two daughter cells.

    • In plant cells, cytokinesis occurs through the formation of a cell plate, which is made up of vesicles containing cell wall material. The cell plate grows outward until it fuses with the existing cell wall, dividing the cell into two daughter cells.

  • Question 3: During which stages of the cell cycle does a chromosome consist of two identical chromatids?

    • A chromosome consists of two identical chromatids during the S phase of the cell cycle, when DNA replication occurs.

  • Question 4: Compare the roles of tubulin and actin during eukaryotic cell division with the roles of tubulin-like and actin-like proteins during bacterial binary fission.

    • Tubulin and actin play important roles in eukaryotic cell division. Tubulin forms microtubules, which are involved in the formation of the mitotic spindle and the separation of chromosomes. Actin is involved in cytokinesis, helping to form the cleavage furrow or cell plate.

    • In bacterial binary fission, tubulin-like and actin-like proteins are involved in a similar manner. They polymerize to form filaments that help in the separation of daughter chromosomes and the division of the bacterial cell.

  • Question 5: A kinetochore has been compared to a coupling device that connects a motor to the cargo that it moves. Explain.

    • A kinetochore is a protein structure located on the centromere of a chromosome. It serves as a connection point for microtubules of the mitotic spindle, similar to how a coupling device connects a motor to the cargo it moves. The kinetochore helps to move and align the chromosomes during cell division.

  • Question 6: What other functions do actin and tubulin carry out? Name the proteins they interact with to do so.

    • Actin and tubulin have other functions in addition to their roles in cell division.

    • Actin interacts with myosin to generate muscle contractions and is involved in cell movement and shape changes.

    • Tubulin interacts with various proteins to form structures like cilia and flagella, which are involved in cell motility.

Concept 12.3 The eukaryotic cell cycle is regulated by a molecular control system

  • The timing and rate of cell division in different parts of a plant or animal are crucial to normal growth, development, and maintenance.

  • The frequency of cell division varies with the type of cell.

  • Regulation at the molecular level controls cell cycle differences in different cell types.

  • Understanding the mechanisms of cell cycle regulation is important for understanding normal cell cycles and cancer cell behavior.

The Cell Cycle Control System

  • The cell cycle is driven by specific signaling molecules present in the cytoplasm.

  • Experiments with mammalian cells grown in culture provided evidence for the presence of signaling molecules.

  • Fusion experiments showed that the cell cycle events can be triggered in a cell by the cytoplasm of another cell in a different phase of the cell cycle.

  • The cell cycle control system is a cyclically operating set of molecules that directs the sequential events of the cell cycle.

Mechanisms of cell division in several groups of organisms

  • Different organisms have different mechanisms of cell division.

  • Bacteria use binary fission, where the daughter chromosomes move to opposite ends of the cell.

  • Diatoms and some yeasts have a spindle formed within the nucleus, and the nuclear envelope remains intact during cell division.

  • Most eukaryotes, including plants and animals, have a spindle that forms outside the nucleus, and the nuclear envelope breaks down during mitosis.

  • Dinoflagellates have chromosomes that attach to the intact nuclear envelope, and microtubules pass through the nucleus inside cytoplasmic tunnels.

Video: Nuclear Envelope Breakdown and Formation During Mitosis in C. elegans, a Eukaryote

  • The video demonstrates the breakdown and formation of the nuclear envelope during mitosis in the eukaryote C. elegans.

Page 12: The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

  • Rhythmic fluctuations in the abundance and activity of cell cycle control molecules pace the sequential events of the cell cycle.

  • Regulatory molecules are mainly proteins of two types: protein kinases and cyclins.

    • Protein kinases activate or inactivate other proteins by phosphorylating them.

    • Cyclins are proteins that fluctuate in concentration throughout the cell cycle.

  • Cyclin-dependent kinases (Cdks) are kinases that are attached to cyclins to be active.

  • The activity of a Cdk rises and falls with changes in the concentration of its cyclin partner.

  • MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers the cell's passage into the M phase.

Cell Cycle Checkpoints

  • The cell cycle control system has checkpoints where stop and go-ahead signals can regulate the cycle.

  • Three important checkpoints are found in the G1, G2, and M phases.

  • The cell cycle is regulated at these checkpoints by both internal and external signals.

Page 15: Inquiry Do molecular signals in the cytoplasm regulate the cell cycle? experiment

  • Researchers at the University of Colorado conducted an experiment to investigate whether cytoplasmic molecules control the progression of the cell cycle.

  • They induced cultured mammalian cells at different phases of the cell cycle to fuse.

  • When a cell in the S phase was fused with a cell in G1, the G1 nucleus immediately entered the S phase and DNA was synthesized.

  • When a cell in the M phase was fused with a cell in G1, the G1 nucleus immediately began mitosis, even though the chromosomes had not been duplicated.

Conclusion

  • The results suggest that molecules present in the cytoplasm during the S or M phase control the progression to those phases.

Animation: Control of the Cell Cycle

  • The animation provides a visual representation of the control of the cell cycle.

Page 13:

  • MPF helps switch itself off during anaphase by initiating a process that leads to the destruction of its own cyclin

    • The noncyclin part of MPF, the Cdk, persists in the cell, inactive until it becomes part of MPF again by associating with new cyclin molecules synthesized during the S and G2 phases of the next round of the cycle

  • The fluctuating activities of different cyclin-Cdk complexes are important in controlling all stages of the cell cycle and give go-ahead signals at some checkpoints

  • MPF controls the cell's passage through the G2 checkpoint

  • The activity of cyclin-Cdk protein complexes regulates cell behavior at the G1 checkpoint

  • Animal cells have at least three Cdk proteins and several different cyclins that operate at the G1 checkpoint

Stop and Go Signs: Internal and External Signals at the Checkpoints:

  • Animal cells have built-in stop signals that halt the cell cycle at checkpoints until overridden by go-ahead signals

  • Signals at checkpoints come from cellular surveillance mechanisms inside the cell and from outside the cell

  • Three important checkpoints are the G1, G2, and M phases

  • The G1 checkpoint is the most important, if a cell receives a go-ahead signal at this checkpoint, it will usually complete the cell cycle and divide

  • If a cell does not receive a go-ahead signal at the G1 checkpoint, it may exit the cycle and enter the G0 phase

  • Most cells of the human body are in the G0 phase

  • Mature nerve cells and muscle cells never divide, while other cells like liver cells can be "called back" from the G0 phase to the cell cycle by external cues

Molecular mechanisms that help regulate the cell cycle:

  • The pathways that link signals originating inside and outside the cell with the responses by cyclin-dependent kinases and other proteins are still being studied

  • An internal signal occurs at the M checkpoint, where anaphase does not begin until all the chromosomes are properly attached to the spindle

  • Unattached kinetochores to spindle microtubules delay anaphase, and only when all kinetochores are properly attached does the appropriate regulatory protein complex become activated

  • MPF acts as a kinase and indirectly activates other kinases

  • MPF causes phosphorylation of various proteins of the nuclear lamina, promoting fragmentation of the nuclear envelope during prometaphase

  • MPF contributes to molecular events required for chromosome condensation and spindle formation during prophase

Page 14:

  • External factors can influence cell division

    • Cells fail to divide if an essential nutrient is lacking in the culture medium

    • Most types of mammalian cells divide in culture only if the growth medium includes specific growth factors

  • Platelet-derived growth factor (PDGF) stimulates fibroblast division

    • PDGF molecules bind to receptor tyrosine kinases on the plasma membranes of cells

    • This triggers a signal transduction pathway that allows cells to pass the G1 checkpoint and divide

    • PDGF is released by platelets in the vicinity of an injury, promoting fibroblast proliferation to help heal the wound

  • Density-dependent inhibition and anchorage dependence regulate cell division

    • Crowded cells stop dividing (density-dependent inhibition)

    • Cells must be attached to a substratum to divide (anchorage dependence)

    • Cell-surface protein binding between adjacent cells sends a signal that inhibits cell division

Page 15:

  • Cancer cells exhibit loss of cell cycle controls

    • They do not stop dividing when growth factors are depleted

    • Cancer cells can go on dividing indefinitely and do not exhibit density-dependent inhibition or anchorage dependence

  • Differences between normal cells and cancer cells

    • Cancer cells stop dividing at random points in the cell cycle, rather than at the normal checkpoints

    • Cancer cells may have abnormalities in the signaling pathway or the cell cycle control system

    • Mutations in genes can alter the function of protein products, resulting in faulty cell cycle control

Page 16: The Cell Cycle and Malignant Tumors

  • Malignant tumors show changes in cells beyond excessive proliferation

    • Unusual numbers of chromosomes may be present

    • Debate on whether this is a cause or effect of tumor-related changes

    • Altered metabolism and loss of constructive function

    • Abnormal changes on cell surface cause cancer cells to lose attachments to neighboring cells and extracellular matrix

    • Spread of cancer cells into nearby tissues

    • Secretion of signaling molecules that cause blood vessels to grow toward the tumor

    • Some tumor cells separate from the original tumor, enter blood vessels and lymph vessels, and travel to other parts of the body

    • Formation of new tumors in other parts of the body is called metastasis

  • Treatment options for localized tumors and metastatic tumors

    • Localized tumors can be treated with high-energy radiation that damages DNA in cancer cells more than normal cells

    • Majority of cancer cells have lost the ability to repair DNA damage

    • Metastatic tumors are treated with chemotherapy

    • Chemotherapeutic drugs interfere with specific steps in the cell cycle

    • Example: Taxol freezes the mitotic spindle, preventing cell division and leading to destruction of actively dividing cells

    • Side effects of chemotherapy due to effects on normal cells that divide frequently

    • Nausea, hair loss, susceptibility to infection are common side effects

Cancer Cell Behavior and Metastasis

  • Cancer cells invade neighboring tissue

  • Tumor grows from a single cancer cell

  • Cancer cells spread through lymph and blood vessels to other parts of the body

  • A small percentage of cancer cells may metastasize to another part of the body

Figure 12.20: Growth and Metastasis of a Malignant Breast Tumor

  • Genetic and cellular changes contribute to a tumor becoming malignant

  • Malignant tumor cells grow uncontrollably and can spread to neighboring tissues and other parts of the body

  • Metastasis is the spread of cancer cells beyond their original site

Cell Transformation and Abnormal Cell Behavior

  • Cells in culture can divide indefinitely if given a continual supply of nutrients

  • Example: HeLa cells, derived from a tumor removed from Henrietta Lacks in 1951

  • Transformation causes cells to behave like cancer cells

  • Normal mammalian cells in culture divide only about 20 to 50 times before stopping and dying

  • Cancer cells evade normal controls that trigger apoptosis when something is wrong

  • Abnormal cell behavior can be catastrophic in the body

Benign Tumors vs Malignant Tumors

  • Single cell in tissue undergoes steps to convert to a cancer cell

  • Immune system recognizes and destroys abnormal cells, but some may evade destruction

  • Proliferation of abnormal cells leads to the formation of a tumor

  • Benign tumors remain at the original site and can be removed by surgery

  • Malignant tumors include cells that can spread to new tissues and impair organ functions

  • Malignant tumors are also called transformed cells

  • Individual with a malignant tumor is said to have cancer

Page 17:

  • Medical treatments for cancer aim to block the cell cycle of cancerous tumor cells

  • Cell cycle inhibitors derived from human umbilical cord stem cells can be used as potential treatments

  • A study was conducted using human glioblastoma cells to determine where in the cell cycle the inhibitor blocks the division of cancer cells

  • The cells were treated with a fluorescent chemical and run through a flow cytometer to analyze the DNA content

  • The data was plotted in histograms to compare the control sample and the treated sample

Interpreting Histograms

  1. The histograms show the distribution of cells based on the amount of fluorescence, which indirectly represents the relative amount of DNA per cell

    • The x-axis represents the amount of fluorescence per cell

  2. In the control sample histogram:

    • The first peak (region A) represents cells with a lower amount of DNA per cell

    • The second peak (region C) represents cells with a higher amount of DNA per cell

  3. In the control sample histogram:

    • The population of cells in region A is in the G1 phase of the cell cycle

    • The population of cells in region C is in the G2 phase of the cell cycle

    • The S phase population of cells does not show a distinct peak in the histogram

  4. The treated sample histogram shows the effect of growing cancer cells alongside human umbilical cord stem cells that produce the potential inhibitor

    • The histogram should be labeled with the cell cycle phases

    • The phase with the greatest number of cells in the treated sample should be identified

    • The distribution of cells among G1, S, and G2 phases in the control and treated samples should be compared

    • A mechanism by which the stem cell-derived inhibitor might arrest the cancer cell cycle at a specific stage should be proposed

Concept Check 12.3

  1. Figure 12.14 shows nuclei resulting from experiment 2 containing different amounts of DNA because different treatments were applied to the cells, affecting DNA replication.

  2. MpF allows a cell to pass the G2 phase checkpoint and enter mitosis by activating cyclin-dependent kinases (CDKs) that phosphorylate target proteins involved in mitosis.

  3. Receptor tyrosine kinases and intracellular receptors can function in triggering cell division by activating signaling pathways that lead to cell cycle progression.

Interview with Bruce Alberts: Cancer control and careers in science

  • Bruce Alberts discusses the importance of understanding the molecular basis of cancer for developing effective treatments

  • He emphasizes the need for interdisciplinary collaboration in cancer research

  • Alberts highlights the role of basic research in uncovering fundamental mechanisms of cancer

BBC Video: Are Fruit Flies the key in the Fight Against Cancer?

  • The video explores how fruit flies are used as model organisms in cancer research

  • Fruit flies share many genes and biological processes with humans, making them valuable for studying cancer

  • Researchers use fruit flies to identify genes involved in cancer development and test potential treatments

Page 18:

  • The mitotic spindle, made up of microtubules, controls chromosome movement during mitosis.

    • In animal cells, it arises from the centrosomes and includes spindle microtubules and asters.

    • Some spindle microtubules attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate.

    • After sister chromatids separate, motor proteins move them along kinetochore microtubules toward opposite ends of the cell.

    • The cell elongates when motor proteins push nonkinetochore microtubules from opposite poles away from each other.

  • Mitosis is usually followed by cytokinesis.

    • Animal cells carry out cytokinesis by cleavage.

    • Plant cells form a cell plate.

  • During binary fission in bacteria, the chromosome replicates and the daughter chromosomes actively move apart.

    • Some of the proteins involved in bacterial binary fission are related to eukaryotic actin and tubulin.

  • Mitosis likely evolved from prokaryotic cell division.

  • Certain unicellular eukaryotes exhibit mechanisms of cell division that may be similar to those of ancestors of existing eukaryotes.

    • Such mechanisms might represent intermediate steps in the evolution of mitosis.

  • Chromosomes exist as single DNA molecules in the S phase of interphase and the stages of mitosis.

ConCept 12.3 the eukaryotic cell cycle is regulated by a molecular control system (pp. 244–250):

  • Signaling molecules present in the cytoplasm regulate progress through the cell cycle.

  • The cell cycle control system is molecularly based.

  • Cyclic changes in regulatory proteins work as a cell cycle clock.

  • The key molecules are cyclins and cyclin-dependent kinases (Cdks).

  • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received.

  • Important checkpoints occur in G1, G2, and M phases.

  • Both internal signals and external signals control the cell cycle checkpoints via signal transduction pathways.

  • Most cells exhibit density-dependent inhibition of cell division as well as anchorage dependence.

  • Cancer cells elude normal cell cycle regulation and divide unchecked, forming tumors.

  • Malignant tumors invade nearby tissues and can undergo metastasis, exporting cancer cells to other sites, where they may form secondary tumors.

  • Recent cell cycle and cell signaling research, and new techniques for sequencing DNA, have led to improved cancer treatments.

test youR unDeRstAnDInG level 1: Knowledge/Comprehension:

  • Through a microscope, you can see a cell plate beginning to develop across the middle of a cell and nuclei forming on either side of the cell plate.

    • This cell is most likely a plant cell in the process of cytokinesis.

suMMARy oF Key ConCepts:

  • Unicellular organisms reproduce by cell division; multicellular organisms depend on cell division for their development from a fertilized egg and for growth and repair.

  • Cell division is part of the cell cycle, an ordered sequence of events in the life of a cell.

ConCept 12.1 Most cell division results in genetically identical daughter cells (pp. 235–237):

  • The genetic material (DNA) of a cell—its genome—is partitioned among chromosomes.

  • Each eukaryotic chromosome consists of one DNA molecule associated with many proteins.

  • Together, the complex of DNA and associated proteins is called chromatin.

  • The chromatin of a chromosome exists in different states of condensation at different times.

  • In animals, gametes have one set of chromosomes and somatic cells have two sets.

  • Cells replicate their genetic material before they divide, each daughter cell receiving a copy of the DNA.

  • Prior to cell division, chromosomes are duplicated.

  • Each one then consists of two identical sister chromatids joined along their lengths by sister chromatid cohesion and held most tightly together at a constricted region at the centromeres.

  • When this cohesion is broken, the chromatids separate during cell division, becoming the chromosomes of the daughter cells.

  • Eukaryotic cell division consists of mitosis (division of the nucleus) and cytokinesis (division of the cytoplasm).

ConCept 12.2 the mitotic phase alternates with interphase in the cell cycle (pp. 237–244):

  • Between divisions, a cell is in interphase: the G1, S, and G2 phases.

  • The cell grows throughout interphase, with DNA being replicated only during the synthesis (S) phase.

  • Mitosis and cytokinesis make up the mitotic (M) phase

JD

Campbell Chapter 12 - The Cell Cycle

Page 1:

  • Key Concepts 12.1, 12.2, and 12.3

  • Cell division is the ability of organisms to produce more of their own kind

  • Rudolf Virchow's concept of "Omnis cellula e cellula"

  • Cell division plays important roles in reproduction, development, and renewal/repair

  • The cell cycle and its phases

  • The distribution of chromosomes to daughter cells during cell division

Page 2:

  • Chapter 12: The Cell Cycle

  • The cell division process is part of the cell cycle

  • Passing identical genetic material to cellular offspring is a crucial function of cell division

  • Most cell division results in genetically identical daughter cells

  • DNA replication and distribution in cell division

  • Chromosomes and their structure

  • Characteristics of eukaryotic chromosomes

  • The number of chromosomes in different eukaryotic species

Page 3:

  • Mitosis is the division of genetic material in the nucleus

    • Followed immediately by cytokinesis, the division of the cytoplasm

    • Results in two cells that are genetically equivalent to the parent cell

  • From a fertilized egg, mitosis and cytokinesis produce somatic cells

    • Somatic cells have 23 pairs of chromosomes, one set inherited from each parent

  • Reproductive cells, or gametes, have half as many chromosomes as somatic cells

    • Human gametes have one set of 23 chromosomes

  • The number of chromosomes in somatic cells varies among species

Distribution of Chromosomes During Eukaryotic Cell Division:

  • When a cell is not dividing, each chromosome is in the form of a long, thin chromatin fiber

  • After DNA replication, the chromosomes condense as part of cell division

    • Chromosomes become densely coiled and folded, visible with a light microscope

  • Each duplicated chromosome consists of two sister chromatids

    • Sister chromatids are joined copies of the original chromosome

  • Sister chromatids are attached all along their lengths by protein complexes called cohesins

  • Each sister chromatid has a centromere, a region where it is attached most closely to its sister chromatid

  • Later in the cell division process, sister chromatids separate and move into two new nuclei

  • Once separated, sister chromatids are considered individual chromosomes

  • This step essentially doubles the number of chromosomes during cell division

Figure 12.4:

  • Shows a highly condensed, duplicated human chromosome

  • Chromosome duplication and condensation occur during cell division

  • Each duplicated chromosome consists of two sister chromatids connected by sister chromatid cohesion

  • Sister chromatids contain a copy of the DNA molecule

  • Molecular and mechanical processes separate sister chromatids into two chromosomes and distribute them to daughter cells

Figure 12.5:

  • Illustrates chromosome duplication and distribution during cell division

  • Asks how many chromatid arms the chromosome in Figure 2 has

  • Shows the point where one chromosome becomes two

BioFlix® Animation: Chromosome Duplication:

  • Provides an animation of chromosome duplication during cell division

Page 4:

  • The cell cycle consists of four phases: G1, S, G2, and M.

    • G1 is the growth phase where the cell continues to grow.

    • S is the synthesis phase where DNA replication occurs.

    • G2 is the phase where the cell completes preparations for cell division.

    • M is the phase where the cell divides.

  • The duration of each phase varies in different types of cells.

    • The M phase occupies less than 1 hour.

    • The S phase occupies 10-12 hours, about half the cycle.

    • The G1 and G2 phases together occupy the rest of the time.

  • Some cells in a multicellular organism divide infrequently or not at all and spend their time in G1 or G0 phase.

  • Mitosis is conventionally broken down into five stages: prophase, prometaphase, metaphase, anaphase, and telophase.

  • Cytokinesis completes the mitotic phase.

Page 4-5:

  • The mitotic spindle, made of microtubules, plays a crucial role in mitosis.

  • Meiosis is a variation of cell division that produces gametes with half the number of chromosomes as the parent cell.

  • Meiosis in humans occurs in special cells in the ovaries or testes.

  • Fertilization fuses two gametes together and restores the chromosome number.

  • Mitosis conserves the chromosome number in every somatic cell nucleus of the new individual.

  • The remainder of the chapter focuses on mitosis and the cell cycle in eukaryotes.

Page 5:

  • Mitosis is just one part of the cell cycle, which also includes interphase.

  • Interphase is a much longer stage that accounts for about 90% of the cell cycle.

  • Interphase can be divided into three phases: G1, S, and G2.

  • During interphase, the cell grows by producing proteins and cytoplasmic organelles.

  • Mitosis and cytokinesis make up the mitotic phase of the cell cycle.

  • Mitosis distributes the daughter chromosomes to daughter nuclei, while cytokinesis divides the cytoplasm to produce two daughter cells.

Page 5:

  • Prophase is the first stage of mitosis where chromatin fibers condense into discrete chromosomes.

  • The nucleoli disappear, and the mitotic spindle begins to form.

  • Prometaphase is the stage where the nuclear envelope fragments, and microtubules invade the nuclear area.

  • The chromosomes become even more condensed, and kinetochores form at the centromere of each chromatid.

  • Microtubules attach to the kinetochores and jerk the chromosomes back and forth.

  • Nonkinetochore microtubules interact with those from the opposite pole of the spindle, lengthening the cell.

Page 6:

Main ideas:

  • Metaphase: centrosomes at opposite poles, chromosomes at metaphase plate, kinetochores attached to microtubules

  • Anaphase: cohesin proteins cleaved, sister chromatids become independent chromosomes, chromosomes move towards opposite ends of the cell

  • Telophase and Cytokinesis: daughter nuclei form, nuclear envelopes arise, nucleoli reappear, chromosomes become less condensed, remaining spindle microtubules depolymerized, division of cytoplasm begins

Supporting details:

  • Metaphase:

    • Centrosomes at opposite poles of the cell

    • Chromosomes at the metaphase plate, with centromeres at the plate

    • Kinetochores of sister chromatids attached to kinetochore microtubules from opposite poles

  • Anaphase:

    • Shortest stage of mitosis

    • Cohesin proteins cleaved, allowing sister chromatids to separate

    • Daughter chromosomes move towards opposite ends of the cell as kinetochore microtubules shorten

    • Centromeres are pulled ahead of the arms, moving at a rate of about 1 µm/min

    • Cell elongates as nonkinetochore microtubules lengthen

    • By the end of anaphase, both ends of the cell have complete collections of chromosomes

  • Telophase and Cytokinesis:

    • Two daughter nuclei form in the cell

    • Nuclear envelopes form from fragments of the parent cell's nuclear envelope and other portions of the endomembrane system

    • Nucleoli reappear

    • Chromosomes become less condensed

    • Remaining spindle microtubules are depolymerized

    • Mitosis is complete, resulting in the division of one nucleus into two genetically identical nuclei

    • Cytokinesis begins, resulting in the division of the cytoplasm

    • In animal cells, cytokinesis involves the formation of a cleavage furrow

Page 7:

Main ideas:

  • Structure and function of the spindle during anaphase

  • Spindle microtubules elongate and shorten

  • Centrosomes and centrioles in animal cells

  • Kinetochore microtubules and movement of chromosomes

  • Metaphase plate and interaction of microtubules

Supporting details:

  • Structure and function of the spindle during anaphase:

    • Spindle correlates well with its function during anaphase

    • Anaphase begins when cohesins holding sister chromatids are cleaved by separase

    • Chromatids become individual chromosomes that move towards opposite ends of the cell

  • Spindle microtubules elongate and shorten:

    • Spindle microtubules elongate by incorporating more subunits of the protein tubulin

    • Spindle microtubules shorten by losing subunits

  • Centrosomes and centrioles in animal cells:

    • Spindle microtubules assemble at the centrosome, a subcellular region that organizes the cell's microtubules

    • Centrosome contains a pair of centrioles, but they are not essential for cell division

    • Centrioles are not present in plant cells, which still form mitotic spindles

  • Kinetochore microtubules and movement of chromosomes:

    • Each sister chromatid of a duplicated chromosome has a kinetochore

    • Kinetochore microtubules attach to kinetochores during prometaphase

    • Chromosomes move towards the pole from which the microtubules extend

    • Movement stops when microtubules from the opposite pole attach to the kinetochore on the other chromatid

    • Chromosome moves back and forth before settling midway between the two ends of the cell

  • Metaphase plate and interaction of microtubules:

    • Metaphase plate is a plane midway between the spindle's two poles

    • Metaphase plate is an imaginary plate, not an actual cellular structure

    • Microtubules that do not attach to kinetochores elongate and overlap with other nonkinetochore microtubules from the opposite pole

    • Asters, radial arrays of short microtubules, extend from each centrosome

Page 8: The Cell Cycle

Kinetochore microtubules function in poleward movement of chromosomes

  • Two mechanisms involving motor proteins are at play

  • Motor proteins on kinetochores "walk" chromosomes along microtubules

  • Microtubules depolymerize at kinetochore ends after motor proteins pass

  • Chromosomes are also "reeled in" by motor proteins at spindle poles

  • Microtubules depolymerize after passing by motor proteins at poles

  • Both mechanisms are used, with varying contributions among cell types

Nonkinetochore microtubules elongate the whole cell during anaphase

  • Responsible for elongating the cell during anaphase

  • Nonkinetochore microtubules from opposite poles overlap during metaphase

  • Motor proteins attached to microtubules walk them away from each other

  • Microtubules push apart, elongating the cell

  • Microtubules lengthen by the addition of tubulin subunits to their ends

  • Duplicate groups of chromosomes arrive at opposite ends of the cell

Cytokinesis in animal cells occurs through cleavage

  • Cleavage furrow appears near the old metaphase plate

  • Contractile ring of actin microfilaments and myosin molecules forms

  • Actin microfilaments interact with myosin, causing the ring to contract

  • Cleavage furrow deepens until the parent cell is pinched in two

  • Produces two completely separated cells with their own nucleus and cytosol

Cytokinesis in plant cells involves the formation of a cell plate

  • No cleavage furrow

  • Vesicles from the Golgi apparatus move to the middle of the cell

  • Vesicles coalesce to form a cell plate

  • Cell wall materials are deposited along the cell plate

  • Eventually, the cell plate becomes the new cell wall

Page 9: Inquiry - At which end do kinetochore microtubules shorten during anaphase?

Experiment by Gary Borisy and colleagues

  • Labeled microtubules of a pig kidney cell in early anaphase with a yellow fluorescent dye

  • Marked a region of the kinetochore microtubules between one spindle pole and the chromosomes

  • Used a laser to eliminate fluorescence from the marked region

  • Monitored changes in microtubule length on either side of the mark

Results of the experiment

  • Microtubule segments on the kinetochore side of the mark shortened

  • Microtubule segments on the spindle pole side stayed the same length

Conclusion of the experiment

  • Chromosome movement is correlated with kinetochore microtubules shortening at their kinetochore ends

  • Microtubules depolymerize at kinetochore ends, releasing tubulin subunits

  • Supports the hypothesis that chromosomes are walked along microtubules during anaphase

Page 9: Animation - Microtubule Depolymerization

  • Animation demonstrating the process of microtubule depolymerization during anaphase

Page 9:

  • Cytokinesis in animal and plant cells

    • Animal cells: cleavage of the cell through a cleavage furrow

    • Plant cells: formation of a cell plate

      • Vesicles carrying cell wall material collect inside the cell plate

      • Cell plate enlarges and fuses with the plasma membrane

      • Two daughter cells are formed, each with its own plasma membrane

      • A new cell wall forms between the daughter cells

  • Binary fission in bacteria

    • Bacteria and archaea can undergo binary fission

    • Binary fission refers to the process of cell division in half

    • Bacterial binary fission does not involve mitosis

    • Bacterial chromosomes are circular DNA molecules

    • Replication of bacterial chromosomes and distribution to daughter cells is a challenge

    • DNA replication starts at the origin of replication

    • One origin moves towards the opposite end of the cell as replication continues

    • Cell elongates during replication

    • When replication is complete and the cell has doubled in size, the plasma membrane pinches inward, dividing the cell into two daughter cells

    • Bacterial chromosomes move similar to the movement of centromeres in eukaryotic chromosomes during anaphase of mitosis

    • Proteins play important roles in bacterial chromosome movement and cell division

Page 10:

  • The evolution of mitosis

    • Mitosis may have evolved from simpler prokaryotic mechanisms of cell reproduction

    • Proteins involved in bacterial binary fission are related to eukaryotic proteins involved in mitosis

    • Variations of cell division exist in different organisms

    • Unicellular eukaryotes such as dinoflagellates, diatoms, and some yeasts have nuclear division processes that resemble ancestral mechanisms

    • Nuclear envelope remains intact during these types of nuclear division

    • Hypothesis uses currently existing species as examples and ignores potential intermediate mechanisms used by extinct species

Page 11:

  • Question 1: How many chromosomes are shown in the illustration in Figure 12.8? Are they duplicated? How many chromatids are shown?

    • The illustration in Figure 12.8 shows 6 chromosomes.

    • The chromosomes are duplicated, as each chromosome consists of two identical chromatids.

  • Question 2: Compare cytokinesis in animal cells and plant cells.

    • In animal cells, cytokinesis occurs through the formation of a cleavage furrow, which pinches the cell membrane inward until the cell is divided into two daughter cells.

    • In plant cells, cytokinesis occurs through the formation of a cell plate, which is made up of vesicles containing cell wall material. The cell plate grows outward until it fuses with the existing cell wall, dividing the cell into two daughter cells.

  • Question 3: During which stages of the cell cycle does a chromosome consist of two identical chromatids?

    • A chromosome consists of two identical chromatids during the S phase of the cell cycle, when DNA replication occurs.

  • Question 4: Compare the roles of tubulin and actin during eukaryotic cell division with the roles of tubulin-like and actin-like proteins during bacterial binary fission.

    • Tubulin and actin play important roles in eukaryotic cell division. Tubulin forms microtubules, which are involved in the formation of the mitotic spindle and the separation of chromosomes. Actin is involved in cytokinesis, helping to form the cleavage furrow or cell plate.

    • In bacterial binary fission, tubulin-like and actin-like proteins are involved in a similar manner. They polymerize to form filaments that help in the separation of daughter chromosomes and the division of the bacterial cell.

  • Question 5: A kinetochore has been compared to a coupling device that connects a motor to the cargo that it moves. Explain.

    • A kinetochore is a protein structure located on the centromere of a chromosome. It serves as a connection point for microtubules of the mitotic spindle, similar to how a coupling device connects a motor to the cargo it moves. The kinetochore helps to move and align the chromosomes during cell division.

  • Question 6: What other functions do actin and tubulin carry out? Name the proteins they interact with to do so.

    • Actin and tubulin have other functions in addition to their roles in cell division.

    • Actin interacts with myosin to generate muscle contractions and is involved in cell movement and shape changes.

    • Tubulin interacts with various proteins to form structures like cilia and flagella, which are involved in cell motility.

Concept 12.3 The eukaryotic cell cycle is regulated by a molecular control system

  • The timing and rate of cell division in different parts of a plant or animal are crucial to normal growth, development, and maintenance.

  • The frequency of cell division varies with the type of cell.

  • Regulation at the molecular level controls cell cycle differences in different cell types.

  • Understanding the mechanisms of cell cycle regulation is important for understanding normal cell cycles and cancer cell behavior.

The Cell Cycle Control System

  • The cell cycle is driven by specific signaling molecules present in the cytoplasm.

  • Experiments with mammalian cells grown in culture provided evidence for the presence of signaling molecules.

  • Fusion experiments showed that the cell cycle events can be triggered in a cell by the cytoplasm of another cell in a different phase of the cell cycle.

  • The cell cycle control system is a cyclically operating set of molecules that directs the sequential events of the cell cycle.

Mechanisms of cell division in several groups of organisms

  • Different organisms have different mechanisms of cell division.

  • Bacteria use binary fission, where the daughter chromosomes move to opposite ends of the cell.

  • Diatoms and some yeasts have a spindle formed within the nucleus, and the nuclear envelope remains intact during cell division.

  • Most eukaryotes, including plants and animals, have a spindle that forms outside the nucleus, and the nuclear envelope breaks down during mitosis.

  • Dinoflagellates have chromosomes that attach to the intact nuclear envelope, and microtubules pass through the nucleus inside cytoplasmic tunnels.

Video: Nuclear Envelope Breakdown and Formation During Mitosis in C. elegans, a Eukaryote

  • The video demonstrates the breakdown and formation of the nuclear envelope during mitosis in the eukaryote C. elegans.

Page 12: The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

  • Rhythmic fluctuations in the abundance and activity of cell cycle control molecules pace the sequential events of the cell cycle.

  • Regulatory molecules are mainly proteins of two types: protein kinases and cyclins.

    • Protein kinases activate or inactivate other proteins by phosphorylating them.

    • Cyclins are proteins that fluctuate in concentration throughout the cell cycle.

  • Cyclin-dependent kinases (Cdks) are kinases that are attached to cyclins to be active.

  • The activity of a Cdk rises and falls with changes in the concentration of its cyclin partner.

  • MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers the cell's passage into the M phase.

Cell Cycle Checkpoints

  • The cell cycle control system has checkpoints where stop and go-ahead signals can regulate the cycle.

  • Three important checkpoints are found in the G1, G2, and M phases.

  • The cell cycle is regulated at these checkpoints by both internal and external signals.

Page 15: Inquiry Do molecular signals in the cytoplasm regulate the cell cycle? experiment

  • Researchers at the University of Colorado conducted an experiment to investigate whether cytoplasmic molecules control the progression of the cell cycle.

  • They induced cultured mammalian cells at different phases of the cell cycle to fuse.

  • When a cell in the S phase was fused with a cell in G1, the G1 nucleus immediately entered the S phase and DNA was synthesized.

  • When a cell in the M phase was fused with a cell in G1, the G1 nucleus immediately began mitosis, even though the chromosomes had not been duplicated.

Conclusion

  • The results suggest that molecules present in the cytoplasm during the S or M phase control the progression to those phases.

Animation: Control of the Cell Cycle

  • The animation provides a visual representation of the control of the cell cycle.

Page 13:

  • MPF helps switch itself off during anaphase by initiating a process that leads to the destruction of its own cyclin

    • The noncyclin part of MPF, the Cdk, persists in the cell, inactive until it becomes part of MPF again by associating with new cyclin molecules synthesized during the S and G2 phases of the next round of the cycle

  • The fluctuating activities of different cyclin-Cdk complexes are important in controlling all stages of the cell cycle and give go-ahead signals at some checkpoints

  • MPF controls the cell's passage through the G2 checkpoint

  • The activity of cyclin-Cdk protein complexes regulates cell behavior at the G1 checkpoint

  • Animal cells have at least three Cdk proteins and several different cyclins that operate at the G1 checkpoint

Stop and Go Signs: Internal and External Signals at the Checkpoints:

  • Animal cells have built-in stop signals that halt the cell cycle at checkpoints until overridden by go-ahead signals

  • Signals at checkpoints come from cellular surveillance mechanisms inside the cell and from outside the cell

  • Three important checkpoints are the G1, G2, and M phases

  • The G1 checkpoint is the most important, if a cell receives a go-ahead signal at this checkpoint, it will usually complete the cell cycle and divide

  • If a cell does not receive a go-ahead signal at the G1 checkpoint, it may exit the cycle and enter the G0 phase

  • Most cells of the human body are in the G0 phase

  • Mature nerve cells and muscle cells never divide, while other cells like liver cells can be "called back" from the G0 phase to the cell cycle by external cues

Molecular mechanisms that help regulate the cell cycle:

  • The pathways that link signals originating inside and outside the cell with the responses by cyclin-dependent kinases and other proteins are still being studied

  • An internal signal occurs at the M checkpoint, where anaphase does not begin until all the chromosomes are properly attached to the spindle

  • Unattached kinetochores to spindle microtubules delay anaphase, and only when all kinetochores are properly attached does the appropriate regulatory protein complex become activated

  • MPF acts as a kinase and indirectly activates other kinases

  • MPF causes phosphorylation of various proteins of the nuclear lamina, promoting fragmentation of the nuclear envelope during prometaphase

  • MPF contributes to molecular events required for chromosome condensation and spindle formation during prophase

Page 14:

  • External factors can influence cell division

    • Cells fail to divide if an essential nutrient is lacking in the culture medium

    • Most types of mammalian cells divide in culture only if the growth medium includes specific growth factors

  • Platelet-derived growth factor (PDGF) stimulates fibroblast division

    • PDGF molecules bind to receptor tyrosine kinases on the plasma membranes of cells

    • This triggers a signal transduction pathway that allows cells to pass the G1 checkpoint and divide

    • PDGF is released by platelets in the vicinity of an injury, promoting fibroblast proliferation to help heal the wound

  • Density-dependent inhibition and anchorage dependence regulate cell division

    • Crowded cells stop dividing (density-dependent inhibition)

    • Cells must be attached to a substratum to divide (anchorage dependence)

    • Cell-surface protein binding between adjacent cells sends a signal that inhibits cell division

Page 15:

  • Cancer cells exhibit loss of cell cycle controls

    • They do not stop dividing when growth factors are depleted

    • Cancer cells can go on dividing indefinitely and do not exhibit density-dependent inhibition or anchorage dependence

  • Differences between normal cells and cancer cells

    • Cancer cells stop dividing at random points in the cell cycle, rather than at the normal checkpoints

    • Cancer cells may have abnormalities in the signaling pathway or the cell cycle control system

    • Mutations in genes can alter the function of protein products, resulting in faulty cell cycle control

Page 16: The Cell Cycle and Malignant Tumors

  • Malignant tumors show changes in cells beyond excessive proliferation

    • Unusual numbers of chromosomes may be present

    • Debate on whether this is a cause or effect of tumor-related changes

    • Altered metabolism and loss of constructive function

    • Abnormal changes on cell surface cause cancer cells to lose attachments to neighboring cells and extracellular matrix

    • Spread of cancer cells into nearby tissues

    • Secretion of signaling molecules that cause blood vessels to grow toward the tumor

    • Some tumor cells separate from the original tumor, enter blood vessels and lymph vessels, and travel to other parts of the body

    • Formation of new tumors in other parts of the body is called metastasis

  • Treatment options for localized tumors and metastatic tumors

    • Localized tumors can be treated with high-energy radiation that damages DNA in cancer cells more than normal cells

    • Majority of cancer cells have lost the ability to repair DNA damage

    • Metastatic tumors are treated with chemotherapy

    • Chemotherapeutic drugs interfere with specific steps in the cell cycle

    • Example: Taxol freezes the mitotic spindle, preventing cell division and leading to destruction of actively dividing cells

    • Side effects of chemotherapy due to effects on normal cells that divide frequently

    • Nausea, hair loss, susceptibility to infection are common side effects

Cancer Cell Behavior and Metastasis

  • Cancer cells invade neighboring tissue

  • Tumor grows from a single cancer cell

  • Cancer cells spread through lymph and blood vessels to other parts of the body

  • A small percentage of cancer cells may metastasize to another part of the body

Figure 12.20: Growth and Metastasis of a Malignant Breast Tumor

  • Genetic and cellular changes contribute to a tumor becoming malignant

  • Malignant tumor cells grow uncontrollably and can spread to neighboring tissues and other parts of the body

  • Metastasis is the spread of cancer cells beyond their original site

Cell Transformation and Abnormal Cell Behavior

  • Cells in culture can divide indefinitely if given a continual supply of nutrients

  • Example: HeLa cells, derived from a tumor removed from Henrietta Lacks in 1951

  • Transformation causes cells to behave like cancer cells

  • Normal mammalian cells in culture divide only about 20 to 50 times before stopping and dying

  • Cancer cells evade normal controls that trigger apoptosis when something is wrong

  • Abnormal cell behavior can be catastrophic in the body

Benign Tumors vs Malignant Tumors

  • Single cell in tissue undergoes steps to convert to a cancer cell

  • Immune system recognizes and destroys abnormal cells, but some may evade destruction

  • Proliferation of abnormal cells leads to the formation of a tumor

  • Benign tumors remain at the original site and can be removed by surgery

  • Malignant tumors include cells that can spread to new tissues and impair organ functions

  • Malignant tumors are also called transformed cells

  • Individual with a malignant tumor is said to have cancer

Page 17:

  • Medical treatments for cancer aim to block the cell cycle of cancerous tumor cells

  • Cell cycle inhibitors derived from human umbilical cord stem cells can be used as potential treatments

  • A study was conducted using human glioblastoma cells to determine where in the cell cycle the inhibitor blocks the division of cancer cells

  • The cells were treated with a fluorescent chemical and run through a flow cytometer to analyze the DNA content

  • The data was plotted in histograms to compare the control sample and the treated sample

Interpreting Histograms

  1. The histograms show the distribution of cells based on the amount of fluorescence, which indirectly represents the relative amount of DNA per cell

    • The x-axis represents the amount of fluorescence per cell

  2. In the control sample histogram:

    • The first peak (region A) represents cells with a lower amount of DNA per cell

    • The second peak (region C) represents cells with a higher amount of DNA per cell

  3. In the control sample histogram:

    • The population of cells in region A is in the G1 phase of the cell cycle

    • The population of cells in region C is in the G2 phase of the cell cycle

    • The S phase population of cells does not show a distinct peak in the histogram

  4. The treated sample histogram shows the effect of growing cancer cells alongside human umbilical cord stem cells that produce the potential inhibitor

    • The histogram should be labeled with the cell cycle phases

    • The phase with the greatest number of cells in the treated sample should be identified

    • The distribution of cells among G1, S, and G2 phases in the control and treated samples should be compared

    • A mechanism by which the stem cell-derived inhibitor might arrest the cancer cell cycle at a specific stage should be proposed

Concept Check 12.3

  1. Figure 12.14 shows nuclei resulting from experiment 2 containing different amounts of DNA because different treatments were applied to the cells, affecting DNA replication.

  2. MpF allows a cell to pass the G2 phase checkpoint and enter mitosis by activating cyclin-dependent kinases (CDKs) that phosphorylate target proteins involved in mitosis.

  3. Receptor tyrosine kinases and intracellular receptors can function in triggering cell division by activating signaling pathways that lead to cell cycle progression.

Interview with Bruce Alberts: Cancer control and careers in science

  • Bruce Alberts discusses the importance of understanding the molecular basis of cancer for developing effective treatments

  • He emphasizes the need for interdisciplinary collaboration in cancer research

  • Alberts highlights the role of basic research in uncovering fundamental mechanisms of cancer

BBC Video: Are Fruit Flies the key in the Fight Against Cancer?

  • The video explores how fruit flies are used as model organisms in cancer research

  • Fruit flies share many genes and biological processes with humans, making them valuable for studying cancer

  • Researchers use fruit flies to identify genes involved in cancer development and test potential treatments

Page 18:

  • The mitotic spindle, made up of microtubules, controls chromosome movement during mitosis.

    • In animal cells, it arises from the centrosomes and includes spindle microtubules and asters.

    • Some spindle microtubules attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate.

    • After sister chromatids separate, motor proteins move them along kinetochore microtubules toward opposite ends of the cell.

    • The cell elongates when motor proteins push nonkinetochore microtubules from opposite poles away from each other.

  • Mitosis is usually followed by cytokinesis.

    • Animal cells carry out cytokinesis by cleavage.

    • Plant cells form a cell plate.

  • During binary fission in bacteria, the chromosome replicates and the daughter chromosomes actively move apart.

    • Some of the proteins involved in bacterial binary fission are related to eukaryotic actin and tubulin.

  • Mitosis likely evolved from prokaryotic cell division.

  • Certain unicellular eukaryotes exhibit mechanisms of cell division that may be similar to those of ancestors of existing eukaryotes.

    • Such mechanisms might represent intermediate steps in the evolution of mitosis.

  • Chromosomes exist as single DNA molecules in the S phase of interphase and the stages of mitosis.

ConCept 12.3 the eukaryotic cell cycle is regulated by a molecular control system (pp. 244–250):

  • Signaling molecules present in the cytoplasm regulate progress through the cell cycle.

  • The cell cycle control system is molecularly based.

  • Cyclic changes in regulatory proteins work as a cell cycle clock.

  • The key molecules are cyclins and cyclin-dependent kinases (Cdks).

  • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received.

  • Important checkpoints occur in G1, G2, and M phases.

  • Both internal signals and external signals control the cell cycle checkpoints via signal transduction pathways.

  • Most cells exhibit density-dependent inhibition of cell division as well as anchorage dependence.

  • Cancer cells elude normal cell cycle regulation and divide unchecked, forming tumors.

  • Malignant tumors invade nearby tissues and can undergo metastasis, exporting cancer cells to other sites, where they may form secondary tumors.

  • Recent cell cycle and cell signaling research, and new techniques for sequencing DNA, have led to improved cancer treatments.

test youR unDeRstAnDInG level 1: Knowledge/Comprehension:

  • Through a microscope, you can see a cell plate beginning to develop across the middle of a cell and nuclei forming on either side of the cell plate.

    • This cell is most likely a plant cell in the process of cytokinesis.

suMMARy oF Key ConCepts:

  • Unicellular organisms reproduce by cell division; multicellular organisms depend on cell division for their development from a fertilized egg and for growth and repair.

  • Cell division is part of the cell cycle, an ordered sequence of events in the life of a cell.

ConCept 12.1 Most cell division results in genetically identical daughter cells (pp. 235–237):

  • The genetic material (DNA) of a cell—its genome—is partitioned among chromosomes.

  • Each eukaryotic chromosome consists of one DNA molecule associated with many proteins.

  • Together, the complex of DNA and associated proteins is called chromatin.

  • The chromatin of a chromosome exists in different states of condensation at different times.

  • In animals, gametes have one set of chromosomes and somatic cells have two sets.

  • Cells replicate their genetic material before they divide, each daughter cell receiving a copy of the DNA.

  • Prior to cell division, chromosomes are duplicated.

  • Each one then consists of two identical sister chromatids joined along their lengths by sister chromatid cohesion and held most tightly together at a constricted region at the centromeres.

  • When this cohesion is broken, the chromatids separate during cell division, becoming the chromosomes of the daughter cells.

  • Eukaryotic cell division consists of mitosis (division of the nucleus) and cytokinesis (division of the cytoplasm).

ConCept 12.2 the mitotic phase alternates with interphase in the cell cycle (pp. 237–244):

  • Between divisions, a cell is in interphase: the G1, S, and G2 phases.

  • The cell grows throughout interphase, with DNA being replicated only during the synthesis (S) phase.

  • Mitosis and cytokinesis make up the mitotic (M) phase