Cell Cycle and Cell Division Notes

Cell Division Functions

Asexual Reproduction:
- A single-celled eukaryote divides into two, each becoming an individual organism.
- Example: Amoeba
Growth and Development:
- A fertilized egg divides, forming multiple cells.
- Example: Sand dollar embryo
Tissue Renewal:
- Dividing bone marrow cells give rise to new blood cells.

Concept 9.1: Genetically Identical Daughter Cells

Cell division involves distributing identical genetic material (DNA) to daughter cells.
Meiosis is an exception, producing sperm and eggs in eukaryotes.
Accuracy in DNA transmission is crucial.
A dividing cell replicates its DNA, distributes copies to opposite ends, and then splits.

Cellular Organization of Genetic Material

A cell's genome is its DNA endowment; prokaryotes usually have a single DNA molecule.
Eukaryotic genomes consist of multiple DNA molecules.
Human cell DNA is about 2 meters long, 250,000 times the cell's diameter.
DNA must be replicated and copies separated for each daughter cell to receive a complete genome.

Chromosomes

DNA molecules are packaged into chromosomes during replication and distribution.
Eukaryotic chromosomes consist of a long, linear DNA molecule associated with proteins.
DNA carries genes, which are units of information specifying an organism's inherited traits.
Associated proteins maintain chromosome structure and control gene activity.
Chromatin is the complex of DNA and proteins, varying in condensation during cell division.
Each eukaryotic species has a characteristic number of chromosomes (e.g., human somatic cells have 46).
Gametes (sperm and eggs) have half the number of chromosomes as somatic cells.

Distribution of Chromosomes During Eukaryotic Cell Division

When a cell is not dividing, chromosomes exist as long, thin chromatin fibers.
After DNA replication, chromosomes condense during cell division.
Chromatin fibers coil and fold, making chromosomes shorter and thicker.

Duplicated Chromosomes

Each duplicated chromosome consists of two sister chromatids, joined copies of the original chromosome.
Sister chromatids are attached along their lengths by cohesins, known as sister chromatid cohesion.
Each sister chromatid has a centromere, a region of repetitive DNA sequences, where it is most closely attached.
Proteins bind to centromeric DNA and condense it, giving the chromosome a narrow "waist".
The part of a chromatid on either side of the centromere is called an arm.
An uncondensed, unduplicated chromosome has a single centromere and two arms.

Separation of Sister Chromatids

During cell division, sister chromatids separate and move into new nuclei at opposite ends of the cell.
Once separated, they are considered individual chromosomes, doubling the chromosome number during cell division.
Each new nucleus receives a chromosome collection identical to the parent cell.

Mitosis and Cytokinesis

Mitosis is the division of genetic material in the nucleus, followed by cytokinesis, the division of the cytoplasm.
One cell becomes two, each genetically equivalent to the parent cell.
Mitosis and cytokinesis produce 37 trillion somatic cells in the human body from a fertilized egg.
These processes continue generating new cells to replace dead or damaged ones.

Meiosis

Gametes (eggs or sperm) are produced by meiosis, a cell division variation.
Meiosis yields daughter cells with only one set of chromosomes (half as many as the parent cell).
In humans, meiosis occurs in ovaries or testes, reducing the chromosome number from 46 to 23.
Fertilization fuses two gametes, returning the chromosome number to 46.
Mitosis conserves this number in every somatic cell nucleus.

Concept Check 9.1

How many chromosomes are drawn in each part of Figure 9.5? (Ignore the micrograph in step 2.)
WHAT IF? A chicken has 78 chromosomes in its somatic cells. How many chromosomes did the chicken inherit from each parent? How many chromosomes are in each of the chicken's gametes? How many chromosomes will be in each somatic cell of the chicken's offspring?

Concept 9.2: Mitotic Phase and Interphase

Mitosis is part of the cell cycle.
Mitotic (M) phase (mitosis and cytokinesis) is the shortest part.
Interphase is a longer stage (about 90% of the cycle), divided into G1, S, and G2 phases.
G phases involve intense metabolic activity and growth.
During interphase, the cell grows, produces proteins and cytoplasmic organelles.
Chromosome duplication occurs entirely during the S phase.
Cell grows (G1), copies chromosomes (S), prepares for division (G2), and divides (M).

Cell Cycle Duration

A human cell might divide in 24 hours.
M phase occupies less than 1 hour, S phase about 10-12 hours.
G2 phase usually takes 4-6 hours; G1 lasts about 5-6 hours.
G1 is most variable in length in different cell types; some cells infrequently divide or not at all, spending their time in G1 (or G0).

Mitosis Stages

Conventionally broken into five stages: prophase, prometaphase, metaphase, anaphase, and telophase.
Cytokinesis overlaps with the latter stages of mitosis.

Mitotic Spindle

Events of mitosis depend on the mitotic spindle, forming in the cytoplasm during prophase.
The spindle consists of fibers made of microtubules and associated proteins.
Cytoskeleton microtubules partially disassemble, providing material to construct the spindle.
Spindle microtubules elongate (polymerize) by incorporating tubulin subunits and shorten (depolymerize) by losing subunits.
In animal cells, spindle microtubule assembly starts at the centrosome.
The centrosome is a subcellular region containing material that organizes the cell's microtubules.
A pair of centrioles is at the center of the centrosome, but they are not essential for cell division.
Centrioles are absent in plant cells, which still form mitotic spindles.

Centrosome Duplication

During interphase in animal cells, the single centrosome duplicates.
Two centrosomes move apart during prophase and prometaphase as spindle microtubules grow out from them.
By the end of prometaphase, two centrosomes are at opposite ends of the cell.
An aster (radial array of short microtubules) extends from each centrosome.
The spindle includes the centrosomes, spindle microtubules, and asters.

Kinetochores

Each of the two sister chromatids has a kinetochore, a protein structure on chromosomal DNA at each centromere.
The kinetochore faces in opposite directions.
During prometaphase, some spindle microtubules attach to kinetochores; these are called kinetochore microtubules.
The number of microtubules attached to a kinetochore varies among species.
The kinetochore acts as a coupling device attaching the spindle to the chromosome.

Mitosis in an Animal Cell

Overview of stages: G2 of Interphase, Prophase, Prometaphase, Metaphase, Anaphase, Telophase and Cytokinesis.

G2 of Interphase

A nuclear envelope encloses the nucleus.
The nucleus contains one or more nucleoli.
Two centrosomes have formed by duplication of a single centrosome; centrosomes organize spindle microtubules and contain two centrioles each.
Chromosomes duplicated during S phase cannot be seen individually because they have not yet condensed.

Prophase

Chromatin fibers become tightly coiled, condensing into discrete chromosomes observable with a light microscope.
Nucleoli disappear.
Each duplicated chromosomes appears as two identical sister chromatids joined at their centromeres.
The mitotic spindle (named for its shape) begins to form- composed of the centrosomes and the microtubules that extend from them.
The radial arrays of shorter microtubules that extend from the centrosomes are called asters.
The centrosomes move away from each other, propelled partly by the lengthening microtubules between them.

Prometaphase

Nuclear envelope fragments.
Microtubules extending from each centrosome can now invade the nuclear area.
Chromosomes have become even more condensed.
A kinetochore (specialized protein structure) has now formed at the centromere of each chromatid (thus, two per chromosome).
Some of the microtubules attach to the kinetochores, becoming "kinetochore microtubules," which jerk the chromosomes back and forth.
Nonkinetochore microtubules interact with those from the opposite pole of the spindle, lengthening the cell.

Metaphase

The centrosomes are now at opposite poles of the cell.
The chromosomes have all arrived at the metaphase plate (plane that is equidistant between the spindle's poles).
The chromosomes' centromeres lie at the metaphase plate.
For each chromosome, the kinetochores of the sister chromatids are attached to kinetochore microtubules coming from opposite poles.

Anaphase

Anaphase is the shortest stage of mitosis, often lasting only a few minutes.
Anaphase begins when the cohesin proteins are cleaved; this allows the two sister chromatids of each pair to part suddenly.
Each chromatids thus becomes an independent chromosome.
The two new daughter chromosomes begin moving toward opposite ends of the cell as their kinetochore microtubules shorten.
Because these microtubules are attached at the centromere region, the centromeres are pulled ahead of the arms, moving at a rate of about 1 μm/min.
The cell elongates as the nonkinetochore microtubules lengthen.
By the end of anaphase, the two ends of the cell have equivalent-and complete-collections of chromosomes.

Telophase

Two daughter nuclei form in the cell; from the fragments of the parent cell's nuclear envelope and other portions of the endomembrane system.
Nucleoli reappear.
The chromosomes become less condensed.
Any remaining spindle microtubules are depolymerized.
Mitosis (the division of one nucleus into two genetically identical nuclei) is now complete.

Cytokinesis

The division of the cytoplasm is usually well under way by late telophase, so the two daughter cells appear shortly after the end of mitosis.
In animal cells, cytokinesis involves the formation of a cleavage furrow, which pinches the cell in two.

Chromosome Movement

When one of a chromosome's kinetochores is captured by microtubules, the chromosome begins to move toward the pole from which those microtubules extend.
This movement comes to a halt as soon as microtubules from the opposite pole attach to the kinetochore on the other chromatid.
The chromosome moves first in one direction and then in the other, back and forth, finally settling midway between the two ends of the cell.
At metaphase, the centromeres of all the duplicated chromosomes are on a plane midway between the spindle's two poles.
This plane is called the metaphase plate, which is an imaginary plate rather than an actual cellular structure.
Microtubules that do not attach to kinetochores have been elongating, and by metaphase they overlap and interact with other nonkinetochore microtubules from the opposite pole of the spindle.
By metaphase, the microtubules of the asters have also grown and are in contact with the plasma membrane.
The spindle is now complete.

Anaphase Initiation

Anaphase begins suddenly when the cohesins holding together the sister chromatids of each chromosome are cleaved by an enzyme called separase.
Once separated, the chromatids become individual chromosomes that move toward opposite ends of the cell.

Kinetochore Microtubule Function

Motor proteins on the kinetochores "walk" the chromosomes along the microtubules, which depolymerize at their kinetochore ends after the motor proteins have passed ("Pac-man" mechanism).
Chromosomes are "reeled in" by motor proteins at the spindle poles and that the microtubules depolymerize after they pass by these motor proteins at the poles.
The general consensus now is that both mechanisms are used and that their relative contributions vary among cell types.

Nonkinetochore Microtubules

In a dividing animal cell, the nonkinetochore microtubules are responsible for elongating the whole cell during anaphase.
Nonkinetochore microtubules from opposite poles overlap each other extensively during metaphase.
During anaphase, the region of overlap is reduced as motor proteins attached to the microtubules walk them away from one another, using energy from ATP.
As the microtubules push apart from each other, their spindle poles are pushed apart, elongating the cell.
At the same time, the microtubules lengthen somewhat by the addition of tubulin subunits to their overlapping ends.
As a result, the microtubules continue to overlap.

Telophase and Cytokinesis

At the end of anaphase, duplicate groups of chromosomes have arrived at opposite ends of the elongated parent cell.
Nuclei re-form during telophase.
Cytokinesis generally begins during anaphase or telophase, and the spindle eventually disassembles by depolymerization of microtubules.

Cytokinesis in Animal Cells

Occurs by cleavage, with a cleavage furrow appearing near the old metaphase plate.
A contractile ring of actin microfilaments associated with myosin molecules forms on the cytoplasmic side of the furrow.
The actin microfilaments interact with myosin molecules, causing the ring to contract.
The cleavage furrow deepens until the parent cell is pinched in two, producing two completely separated cells.

Cytokinesis in Plant Cells

No cleavage furrow; vesicles from the Golgi apparatus move along microtubules to the cell's middle during telophase.
Vesicles coalesce, producing a cell plate; cell wall materials collect inside as it grows.
The cell plate enlarges until its surrounding membrane fuses with the plasma membrane along the perimeter of the cell.
Two daughter cells result, each with its own plasma membrane.
A new cell wall arising from the contents of the cell plate forms between the daughter cells.

Binary Fission in Bacteria

Prokaryotes (bacteria and archaea) reproduce asexually by growing to roughly double their size and then dividing to form two cells.
Most genes are carried on a single bacterial chromosome consisting of a circular DNA molecule and associated proteins.
The cell division process is initiated when the DNA of the bacterial chromosome begins to replicate at a specific place on the chromosome called the origin of replication, producing two origins.
As the chromosome continues to replicate, one origin moves rapidly toward the opposite end of the cell.
While the chromosome is replicating, the cell elongates.
When replication is complete and the bacterium has reached about twice its initial size, proteins cause its plasma membrane to pinch inward, dividing the parent bacterial cell into two daughter cells.
In this way, each cell inherits a complete genome.
Polymerization of one protein resembling eukaryotic actin apparently functions in bacterial chromosome movement during cell division, and another protein that is related to tubulin helps pinch the plasma membrane inward, separating the two bacterial daughter cells.

Evolution of Mitosis

Bacteria, dinoflagellates, diatoms, and some yeasts have variances in mitosis.
Dinoflagellates: Chromosomes attach to the intact nuclear envelope; microtubules pass through the nucleus inside cytoplasmic tunnels.
Diatoms and some yeasts: The microtubules form a spindle within the nucleus; the nuclear envelope remains intact, and the nucleus splits into two daughter nuclei.

Concept Check 9.2

How many chromosomes are shown in the drawing in Figure 9.8? Are they duplicated? How many chromatids are shown?
Compare cytokinesis in animal cells and plant cells.
During which stages of the cell cycle does a chromosome consist of two identical chromatids?
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.

Concept 9.3: Eukaryotic Cell Cycle Regulation

Timing and rate of cell division are crucial for normal growth, development, and maintenance.
Cell division frequency varies with cell type.
Some cells (e.g., nerve and muscle cells) do not divide in mature humans.
Cell cycle differences result from regulation at the molecular level.

Cytoplasmic Signals

Hypothesis: Specific signaling molecules in the cytoplasm drive the cell cycle.
Experiments involving cell fusion demonstrated this; cells in different phases of the cycle were fused.
G1 nucleus entered S phase when fused with a cell in S phase.
A cell undergoing mitosis caused another cell to enter mitosis, even in G1.

Cell Cycle Control System

Sequential cell cycle events are directed by a distinct cyclically operating control system.
This system triggers and coordinates key events.
The cell cycle has checkpoints (control points) where stop and go-ahead signals regulate the cycle.
These signals can be internal (cellular surveillance) or external.
Important checkpoints are in G1, G2, and M phases.

G1 Checkpoint

The G1 checkpoint (restriction point in mammalian cells) seems to be the most important.
Go-ahead signal leads to completion of G1, S, G2, and M phases and division.
No go-ahead signal leads to exiting the cycle into a nondividing state (G0 phase).
Most human body cells are in G0 phase.
Mature nerve and muscle cells never divide.
Other cells (e.g., liver cells) can be called back from G0 by external cues.

Regulatory Proteins

The cell cycle is regulated at the molecular level by a set of regulatory proteins and protein complexes, including proteins called cyclins, and other proteins interacting with cyclins that are kinases
(enzymes that activate or inactivate other proteins by phosphorylating them

Checkpoint Signals

Checkpoint signals can pause or continue the cell cycle clock.
Anaphase, the separation of sister chromatids, does not begin until all the chromosomes are properly attached to the spindle at the metaphase plate.
As long as some kinetochores are unattached to spindle microtubules, the sister chromatids remain together, delaying anaphase.
Only when the kinetochores of all the chromosomes are properly attached to the spindle does the appropriate regulatory protein complex become activated.
Once activated, the complex sets off a Molecular events that activates the enzyme separase, which cleaves the cohesins, allowing the sister chromatids to sepárate.
This mechanism ensures that daughter cells do not end up with missing or extra chromosomes.
there are further checkpoints in S phase and telophase as well.

External Factors Affecting Cell Division

Cells fail to divide if an essential nutrient is lacking in the culture medium.
Most mammalian cells divide in culture only if the growth medium includes specific growth factors.
Growth factors are proteins released by certain cells that stimulate other cells to divide.
Different cell types respond specifically to different growth factors or combinations of growth factors.
Platelet-derived growth factor (PDGF) is made by blood cell fragments called platelets and is required for division of cultured fibroblasts.
Binding of PDGF molecules to fibroblast receptors triggers a signal transduction pathway that allows the cells to pass the G1 checkpoint and divide.
PDGF stimulates fibroblast division not only in the artificial conditions of cell culture but also in an animal's body.
When an injury occurs, platelets release PDGF in the vicinity.
The resulting proliferation of fibroblasts helps heal the wound.

Density-Dependent Inhibition

Density-dependent inhibition is a phenomenon in which crowded cells stop dividing; cultured cells normally divide until they form a single layer.
Binding of a cell-surface protein to its counterpart on an adjoining cell sends a signal that inhibits cell division.

Anchorage Dependence

Most animal cells also exhibit anchorage dependence: To divide, they must be attached to something, such as the inside of a culture flask or the extracellular matrix of a tissue.
Signaled to the cell cycle control system via pathways involving plasma membrane proteins and elements of the cytoskeleton linked to them.
Density-dependent inhibition and anchorage dependence appear to function not only in cell culture but also in the body's tissues, checking the growth of cells at some optimal density and location during embryonic development and throughout an organism's life.

Loss of Cell Cycle Controls in Cancer Cells

Cancer cells do not heed the normal signals that regulate the cell cycle.
Hypothesis: Cancer cells do not need growth factors in their culture medium.
They may make a required growth factor themselves, or they may have an abnormality in the signaling pathway that conveys the growth factor's signal to the cell cycle control system even in the absence of that factor.
Another possibility is an abnormal cell cycle control system.
The underlying basis of the abnormality is almost always a change in one or more genes (for example, a mutation) that alters the function of their protein products, resulting in faulty cell cycle control.
Cancer cells stop dividing at random points, not at normal checkpoints.
Cancer cells can go on dividing indefinitely in culture if they are given a continual supply of nutrients; in essence, they are "immortal."
Cells in culture that acquire the ability to divide indefinitely are said to have undergone a process called transformation, causing them to behave (in cell division, at least) like cancer cells.
Normal cells divide only about 20 to 50 times before they stop dividing, age, and die.
Cancer cells evade apoptosis (programmed cell death).

Tumor Formation

The problem begins when a single cell in a tissue undergoes the first of many steps that converts a normal cell to a cancer cell.
Such a cell often has altered proteins on its surface, and the body's immune system normally recognizes the cell as "nonself"-an insurgent-and destroys it.
If the cell evades destruction, it may proliferate and form a tumor, a mass of abnormal cells within otherwise normal tissue.
Benign Tumor: The abnormal cells may remain at the original site if their genetic and cellular changes don't allow them to move to or survive at another site. Most benign tumors do not cause serious problems and can be removed by surgery.
Malignant Tumor (Cancer): Includes cells whose genetic and cellular changes enable them to spread to new tissues and impair the functions of one or more organs; based on their ability to divide indefinitely in culture, these cells are also sometimes called transformed cells
Malignant tumors grow in an uncontrolled way and can spread to neighboring tissues and, via lymph and blood vessels, to other parts of the body (metastasis).