The cell cycle

What is the cell cycle

the process by which multicellular organisms increase in size and single cell organisms may reproduce

The rate of cell division in single cell

depends largely on how available nutrients are in the surrounding environment. Thus, these organisms tend to grow and divide as fast as they can.

the rate in multicellular

divide only when more cells are needed by the organism.

what are some external factors that impact cell division?

Nutrients, death of nearby cell, release of HGH (human growth hormone) inhibit cell division resulting in dwarfism too much gigantism, Crowding of cells can also inhibit cell division. Another factor that can initiate cell division is the size of the cell; as a cell grows, it becomes inefficient due to its decreasing surface-to volume ratio. The solution to this problem is to divide.

It is essential that the daughter cells produced be

exact duplicates of the parent cell.

Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be

passed forward to every new cell.

 To prevent a compromised cell from continuing to divide, there are

 internal control mechanisms that operate at three main cell cycle checkpoints. A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable. These checkpoints occur near the end of G1, at the G2/M transition, and during metaphase 

The G₁ checkpoint determines

whether all conditions are favorable for cell division to proceed. The G₁ checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process.

What impacts the G1 checkpoint, and what happens if it does not meet the requirements?

External influences, such as growth factors, play a large role in carrying the cell past the G₁ checkpoint. In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G₁ checkpoint. A cell that does not meet all the requirements will not be allowed to progress into the S phase. The cell can halt the cycle and attempt to remedy the problematic condition, or the cell can advance into G₀ and await further signals when conditions improve. 

The G2 checkpoint bars entry into

the mitotic phase if certain conditions are not met. As at  the G1 checkpoint, cell size and protein reserves are assessed. However, the most  important role of the G2 checkpoint is to ensure that all of the chromosomes have been  replicated and that the replicated DNA is not damaged. If the checkpoint mechanisms  detect problems with the DNA, the cell cycle is halted, and the cell attempts to either  complete DNA replication or repair the damaged DNA. 

The M checkpoint occurs near the end of

the metaphase stage of karyokinesis. The M  checkpoint is also known as the spindle checkpoint, because it determines whether all the  sister chromatids are correctly attached to the spindle microtubules. Because the  separation of the sister chromatids during anaphase is an irreversible step, the cycle will  not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to  at least two spindle fibers arising from opposite poles of the cell. 

There are two groups of intracellular molecules that either

promote progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation). These regulatory molecules may act individually, or they can influence the activity or production of other regulatory proteins. Therefore, if more than one mechanism controls the same event, the failure of a single regulator may have almost no effect on the cell cycle. Conversely if the regulator is involved in multiple processes the effect of a deficient or non-functioning regulator can be wide-ranging and possibly fatal to the cell.

Let’s start with Positive Regulation of the Cell Cycle 

Two groups of proteins, called

yclins and cyclin-dependent kinases (Cdks), are responsible for the progress of the cell through the various checkpoints. The levels of the four cyclin proteins fluctuate throughout the cell cycle in a predictable pattern . Increases in the concentration of cyclin proteins are triggered by both external and internal signals. After the cell moves to the next stage of the cell cycle, the cyclins that were active in the previous stage are degraded. 

Cyclins regulate the cell cycle only when

 they are tightly bound to Cdks. While the levels of  Cdk proteins are relatively stable throughout the cell cycle; the concentrations of cyclin  fluctuate and thus, determine when Cdk/cyclin complexes form.

 To be fully active, the  Cdk/cyclin complex must also be

phosphorylated in specific locations. This phosphorylation  is done by other kinases.

Once phosphorylated Cdks in the Cyclin-Cdk complex can 

phosphorylate other proteins. This phosphorylation activates the protein by changing its  shape. The proteins phosphorylated by Cdks are involved in advancing the cell to the next  phase.  

The different cyclins and Cdks bind at specific points in the cell cycle and thus

regulate  different checkpoints. Without a specific concentration of fully activated cyclin/Cdk complexes, the cell cycle cannot proceed through the checkpoints.

 Molecules that prevent the full activation  of Cdks are called

 Cdk inhibitors. Many of these inhibitor molecules directly or indirectly  monitor a particular cell cycle event. The block placed on Cdks by inhibitor molecules will  not be removed until the specific event that the inhibitor monitors is completed. 

The second group of cell cycle regulatory molecules, are negative regulators, molecules  that halt the cell cycle. Remember that in positive regulation, active molecules cause the  cycle to progress. The best understood negative regulatory molecules are

retinoblastoma  protein (Rb), p53 protein, and p21 protein. Retinoblastoma proteins are a group of tumor suppressor proteins common in many cells. The 53 and 21 designations refer to the  functional molecular masses of the proteins (p) in kilodaltons.

All three regulatory molecule proteins, Rb, p53, and p21 act primarily at

the G1  checkpoint. 

p53 is a multi-functional protein that has a major impact on the commitment of a cell to  division because

 it acts when there is damaged DNA in cells that are undergoing the  preparatory processes during G1. p21 expression is controlled by p53 and acts to directly  inhibit Cdks 

When unphosphorylated the p53 which is expressed in the nucleus diffuses out of the  nucleus and is degraded (broken down) by enzymes in the cytosol. IF damaged DNA is  detected, p53 is

phosphorylated by a kinase and is trapped in the nucleus

 As p53 levels  rise, the expression of the p21 protein is triggered. P21 can leave the nucleus, and binds to  and inhibits

the activity of cyclin-CDK complexes, causing the cell cycle to halt

 As a cell is exposed to more stress, higher levels of p53 and p21 accumulate, making it less likely that

the cell will move into the S phase.

 p53 also controls other genes that

 halt the cell cycle and recruit enzymes to repair the DNA. If the DNA cannot be repaired, p53 can trigger apoptosis, or cell suicide, to prevent the duplication of damaged chromosomes. 

Chiefly, Rb monitors - and exerts its influence on

cell size, Rb exerts its regulatory influence on other positive regulator proteins

In the active, dephosphorylated state, Rb binds to

proteins called transcription factors, most commonly, E2F, a critical regulator of the cell cycle. Transcription factors “turn on” specific genes, allowing the production of proteins encoded by that gene. When Rb is bound to E2F, production of proteins necessary for the G₁/S transition is blocked

As the cell increases in size, Rb is slowly phosphorylated until it becomes inactivated by

a change in shape, as a result Rb releases E2F, allowing E2F to now turn on the gene that produces the transition protein, and this particular block is removed (Figure B) and the cell cycle proceeds 

For the cell to move past each of the checkpoints,

all positive regulators must be “turned  on,” and all negative regulators must be “turned off.”  

Rb and other proteins that negatively regulate the cell cycle are sometimes called

tumor suppressors, since unregulated cell division can result in abnormal tissue growth, cancer, and tumors.

Regulation of the cell cycle, or more accurately loss of regulation of the cell cycle can lead  to

cancer, uncontrolled cell growth and the formation of tumors. Thus, Rb, p53 and p21 are  all involved in suppressing the formation of tumors, they help control cell division. 

The rate at which cells divide is dependent on

 the internal signals within the cell as well as external environmental factors.

what are some examples of external enviromental factors

 Cell size, cell resources and cell density are all external factors that influence the rate of cell division.

What are some examples of internal factors

 p53 and p21 are both involved in the inhibition of cyclin/CDK complexes. Rb on the other hand is involved in regulating the transcription of proteins that are needed for cell cycle processes. For the cell cycle to continue the positive regulators (cyclin, CDK) must be active and the negative regulators (Rb, p53, p21) must be inactive.Cyclins are proteins that varying in concentration at different times in the cell cycle. When bound to cyclin dependent kinases (CDKs) they are involved in the phosphorylation of other proteins. This phosphorylation regulates the activity of these other proteins and influences key processes within the cycle.

At which of the cell cycle checkpoints do external conditions have the greatest influence?

1. G₁checkpoint

2. G₂checkpoint

3. M checkpoint

4. G₀ checkpoint

1

Which protein is a positive regulator that phosphorylates other proteins when activated?

1. CDK (cyclin-dependent-kinase)

2. ATP synthase

3. retinoblastoma protein

4. cyclin isomerase

1

Which negative regulatory molecule can trigger cell suicide (apoptosis) if vital cell cycle events do not occur?

1. p53

2. p21

3. retinoblastoma protein (Rb)

4. cyclin-dependent kinase (Cdk)

1

Review: G2 checkpoint

What is the main prerequisite for clearance at the G2 checkpoint?

1. The cell has reached a sufficient size

2. Accurate and complete DNA replication

3. An adequate stockpile of nucleotides

4. Proper attachment of mitotic spindle fibers to kinetochores

2

Review: M checkpoint

If the M checkpoint is not cleared, what stage of mitosis will be blocked?

1. prometaphase

2. prophase

3. metaphase

4. anaphase

4

What is the order of cell division

Interphase: G1, where it grows and carries out normal functions, S phase, (synthesis) where it copies all of its dna, and G2 phase, where it finishes final preparations grows a bit more and checks the DNA

Mitosis (nuclear division): prophase, chromatin condenses into tight, visible chromosomes, and the nuclear envelope starts to break down. Prometaphase sometimes counts as an intermediate step where spindle fibers attach to chromosomes, Metaphase: Chromosomes line up single-file along the middle (equator) of the cell. Anaphase: Sister chromatids are pulled apart toward opposite sides (poles) of the cell by spindle fibers. New nuclear membranes form around each of the two sets of separated chromosomes, and the chromosomes begin to uncoil.

Cytokinesis (cytoplasmic division): the cells cytoplasam splits in half, in animal cells cleveage splits the cells in two and in plant cells a cell plate forms down the middle to build a new wall between the two.

Review: Negative Regulators

The p53 protein stops the cell cycle in response to _________.
Rb, on the other hand, monitors __________.

dna, size.

What proteins are involved in the regulation of the cell cycle and show fluctuations in concentration during the cell cycle?

cyclins

Which of the following are true of protein kinases involved in cell cycle regulation?

 particular proteins kinases give go-ahead signals at G₁ and G₂ checkpoints

 they are enzymes that activate or inactive other proteins

 they function by phosphorylating other proteins

Whether it is a prokaryotic or eukaryotic cell, the replication of the cell must include

 replication of the DNA within the cell.

 The cell’s DNA, packaged as a double-stranded DNA molecule, is called

its genome. 

In prokaryotes, the genome is composed of

 a single, double-stranded DNA molecule in the form of a loop or circle.  

The region in prokaryotic cells containing this genetic material is called

a nucleotide

In addition to the main genome, some prokaryotes also have smaller loops of DNA called

plasmids that are not essential for normal growth.  

However, these plasmids can be exchanged with other bacteria, sometimes resulting in

the acquisition of beneficial new genes that the recipient can add to their chromosomal DNA. Antibiotic resistance is one trait that often spreads through a bacterial colony through plasmid exchange.

A prokaryotes additional non-genomic DNA can be found in:

plasmids

The area where the prokaryotic chromosome is located:

nucleotide

In eukaryotes, the genome consists of

double-stranded linear DNA molecules.

Each species of eukaryotes has a characteristic number of chromosomes in the nuclei of its cells. Human body cells have - gametes have -

Human body cells have 46 chromosomes, while human gametes (sperm or eggs) have 23 chromosomes each.

 A typical body cell, or somatic cell, contains

two matched sets of chromosomes, so there are two copies of each specific chromosome, a configuration known as diploid.

These matched pairs of chromosomes in a diploid organism are called

homologous (“same knowledge”) chromosomes. Homologous chromosomes are the same length and have specific nucleotide segments called genes in exactly the same location, or locus.

 Genes, the functional units of chromosomes, determine specific characteristics by

coding for specific proteins.

Each copy of a homologous pair of chromosomes originates from a different parent; therefore,

the genes themselves are not all identical. The variation of individuals within a species is due to the specific combination of the genes inherited from both parents. Even a slightly altered sequence of nucleotides within a gene can result in an alternate trait.

A diploid cell has_______  the number of chromosomes as a haploid cell.

1. one-fourth

2. half

3. twice

4. four times

3, 1n vs 2n

In the first level of compaction, short stretches of the DNA double helix wrap around

a core of eight histone proteins at regular intervals along the entire length of the chromosome

The DNA-histone complex is called

chromatin.

The beadlike, histone DNA complex is called a

nucleosome,

and DNA connecting the nucleosomes is called

linker dna

The next level of compaction occurs as the nucleosomes and the linker DNA between them are

coiled into a 30-nm chromatin fiber.

In the third level of packing, a variety of - and what do they do within the nucleus?

fibrous proteins is used to pack the chromatin. These fibrous proteins also ensure that each chromosome in a non-dividing cell occupies a particular area of the nucleus that does not overlap with that of any other chromosome.

The first level of DNA organization in a eukaryotic cell is maintained by which molecule?

1. cohesin

2. condensin

3. chromatin

4. histone

4

The single, circular DNA chromosome of bacteria which is not enclosed in a nucleus, is still

packaged to condense its size.  While prokaryotic DNA is associated with proteins that aid in packaging the molecule into a compact size, there are no histone proteins and thus no nucleosomes in prokaryotes.

what proteins pack chromatins and are they present in bacteria as well as eukaryotes?

The packing proteins of bacteria are, however, related to the cohesin and condensin proteins involved in the chromosome compaction of eukaryotes.

Prokaryotes have a - whereas eukaryotes have multiple -

Prokaryotes have a single circular chromosome composed of double-stranded DNA, whereas eukaryotes have multiple, linear chromosomes composed of chromatin surrounded by a nuclear membrane

Cells which have two homologous copies of each chromosome are referred to as being 2n or diploid state. Cells that only have one complete set of chromosomes are said to be n or haploid.  Animal gametes (eggs and sperm) are examples of

haploid cells

 Chromosomes are composed of

 genes, segments of DNA that code for a specific protein

 In diploid organisms half of the chromosomes are inherited from one parent and the homologous set are inherited from the other parent. This means that your diploid cells have

two complete sets of chromosomes from your mother and father for each trait

The condensing complex compacts chromosomes, and the resulting condensed structure is necessary for

 chromosomal segregation during mitosis.

Review: Levels of Eukaryotic Chromosome Structure

Place the following levels in order from the least condensed form to the most condensed form.

____chromatin

____histone wrapping

____DNA strands

____nucleosome formation

dna strands, histone wrapping, nucleosome formation, chromatin

What features are shared by both prokaryotic and eukaryotic genomes? 

Choose all that apply

• there are multiple copies chromosomes

• chromosomes are composed of primarily of DNA

• proteins are involved in the condensed structure

• the chromosomes contain nucleosomes in their condensed form

chromosomes are composed primarily of Dna, proteins are involved in the condensed structure
(the other two do not apply because prokaryotes do not have histones and therefore cannot have nucleosomes and prokaryotes have one set of linear dna)

unlike Eukaryotic cells, chromosomes in prokaryotes are - proteins are used to condense dna in - cells

circular, prokaryotic and eukaryotic cells

within an organism the amount of somantic cells is the same t/f

true

in prokaryotic cells chromosomes are found in the - they also may have - that contain - genes such as the ones that provide -

nucleotide region, plasmid, non essential, antibiotic resistance

what is a somantic cell

any eukaryotic cell that is not a reproductive cell

The process of mitosis moves chromosomes across the cell to separate them. Which of the three cytoskeletal elements is involved in the movement of molecules across the cytoplasm of the cell?

microtubles

a haploid cell has - the number of chromosomes as a diploid cell does.

half

Throughout interphase, nuclear DNA remains in a

semi-condensed chromatin configuration (invisible under microscope).

In the G1 phase (first gap), from a microscopic aspect, little change is visible. However, the cell is quite active at the biochemical level in this phase. In preparation for DNA replication the cell needs to

accumulate the building blocks of chromosomal DNA (nucleotides) and the associated proteins needed for the replication process. In addition, the cell needs to accumulate sufficient energy reserves to complete the task of replicating each chromosome in the nucleus

In the S phase, DNA replication occurs.  Each chromosome is duplicated resulting in identical pairs of DNA molecules

sister chromatids—that are firmly attached to a shared centromere

 During S phase in animal cells the - , which will - is also duplicated

the centrosome, which consists of two centrioles that will aid in cell division, is also duplicated. The resulting two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis.

_ are not present in the centrosomes of other eukaryotic species, such as plants and most fungi.

Centrioles are not present in the centrosomes of other eukaryotic species, such as plants and most fungi. These organisms use other molecules to organize their microtubules during cell division.

Once the DNA is replicated the cell will move into the G₂ phase. Here the cell replenishes its energy stores and

synthesizes proteins necessary for chromosome manipulation (Figure 4). Some cell organelles are also duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic phase and to remove barriers to chromosome movement. There may be additional cell growth during G₂. These final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis.

centriole vs centrosomes

a centrosome contains two centrioles, which are replicated at the end of G1 and beginning of S phase of the cell cycle

Chromosomes are duplicated during what stage of the cell cycle?

1. G1 phase

2. S phase

3. G2 phase

4. M phase

S phase

The mitotic phase is a multistep process that first involves the division of the two sets of chromosomes. This process is referred to as

karyokinese or nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into the two daughter cells. The end result is two identical cells. 

Karyokinesis, also known as mitosis, is divided into a series of phases

prophase, prometaphase, metaphase, anaphase, and telophase—that result in the division of the cell nucleus.

During prophase, the “first phase,” the

nuclear envelope starts to dissociate into small vesicles, and the membranous organelles (such as the Golgi complex or Golgi apparatus, and endoplasmic reticulum), fragment and disperse toward the edges of the cell (Figure 5). The nucleolus disappears (disperses). In animal cells, the centrosomes begin to move to opposite poles of the cell. Microtubules that will form the mitotic spindle extend between the centrosomes (or other structures), pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly with the aid of condensin proteins and become visible under a light microscope.

During prometaphase, the “first change phase,” many processes that were begun in prophase continue to advance

The remnants of the nuclear envelope continue to fragment. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and discrete. Each sister chromatid develops a protein structure called a kinetochore in the centromeric region. The proteins of the kinetochore attract and bind mitotic spindle microtubules. As the spindle microtubules extend, some of these microtubules come into contact with and firmly bind to the kinetochores. Once a mitotic fiber attaches to a chromosome, the chromosome will be oriented until the kinetochores of sister chromatids face the opposite poles. Eventually, all the sister chromatids will be attached via their kinetochores to microtubules from opposing poles.

During metaphase, the “change phase,” all the

chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other by cohesin proteins. At this time, the chromosomes are maximally condensed

During anaphase, the “upward phase,”

the cohesin proteins degrade, and the sister chromatids separate at the centromere. Each chromatid, now called a (daughter) chromosome, is pulled rapidly toward the centrosome to which its microtubule is attached. The cell becomes visibly elongated (oval shaped).

During telophase, the “distance phase,”

the chromosomes reach the opposite poles and begin to decondense (unravel), relaxing into a chromatin configuration. The mitotic spindles are depolymerized into tubulin monomers that will be used to assemble cytoskeletal components for each daughter cell. Nuclear envelopes form around the chromosomes, and nucleosomes appear within the nuclear area (Figure 6).

Please arrange the following into the correct order of events in mitosis from top to bottom.

 

• The chromatin within the nucleus condenses and becomes visible as sister chromatids.

• The kinetochore becomes attached to the mitotic spindle.

• The nucleus reforms and the cell divides.

• Sister chromatids line up at the metaphase plate

• Cohesin proteins break down and the sister chromatids separate

The chromatin within the nucleus condenses and becomes visible as sister chromatids (prophase), the kinetochore becomes attached to the mitotic spindle (prometaphase), sister chromatids line up at the metaphase plate (metaphase), cohesin proteins break down and the sister chromatids separate (anaphase), the nucleus reforms and the cell divides (telophase/cytokenesis).

Separation of the sister chromatids

anaphase

Unpacking of chromosomes and the formation of a new nuclear envelope

telophase

The chromosomes become visible under a light microscope

prophase

The sister chromatids line up in the middle of division plane

metaphase