Cell Cycle Control System

Cell cycle control system
Cell cycle control system directed the sequential events of the cell cycle.
Cell cycle is regulated by checkpoints by both internal and external controls.
A checkpoint in the cell cycle is a critical control point which decides weather
a cell stop and go ahead in a cell cycle. It involves modulation of stop and go-
ahead signals.
There are three major check-points in the cell cycle, G1, G2, and M-phase.
If a cell receives a go-ahead signal at G1 check point, it will usually completes

the S, G2 and M phase and divide.
Or, if it does not receive a go-ahead signal at that point, cell will exist the
cycle and entered into a non-dividing state called the G0 phase.
Most cells of the human-body are actually in the G0 phase ex. Mature nerve-
cells and muscle cells never divide.
Molecular basis for the cell cycle control
This include regulatory proteins, which are of two types:
1. Cyclins
2. Kinases
Cyclins
Cyclins are among the most important core cell cycle regulators.
• Cyclin is a protein and gets its name from its cyclically fluctuating
concentration in the cell.
• There are four basic types found in humans and most other
eukaryotes: G1 cyclins, G1/S cyclins, S cyclins, and M cyclins.
• Each cyclin is associated with a particular phase, transition, or set of
phases in the cell cycle which helps to drive the events of that phase
or period. For example, M cyclin promotes the events of M phase,
such as nuclear envelope breakdown and chromosome
condensation.
• For most of the cell cycle, cyclin is present at low levels, but increases
strongly at the stage where it's needed.
Kinases
• Protein kinases are enzymes that activate or inactivate other proteins

by phosphorylating (attach phosphate group) them.
• Particular protein kinases give the go-ahead signals at the G1 and G2
checkpoints.
• In a growing cell, kinases that involved in the cell cycle are present in
a constant concentration but in a inactive state.
• For their activation, they attached with cyclin.
• As these kinases requires cyclin for their activation they are called as
cyclin-dependent kinases or cdks.
• The activity of cdk rises and falls with the change in concentration of
cyclin.
Cyclin-cdk complex is known as Maturation promoting factor (MPF).
So, MPF consists of two subunits
1. Have kinase activity transfers phosphate group from ATP to specific serine
and threonine residues of specific protein substrates and
2. a regulatory subunit called cyclin
• When the cyclin concentration is low, the kinase lacks the cyclin subunit
and, as a result, is inactive.
• When the cyclin concentration rises, the kinase is activated, causing the
cell to enter M phase.
Cdk-cyclin complex called MPF
Cyclin Regulatory subunit

Kinase activity
Thus,
(1) progression of cells into mitosis depends on an kinase enzyme whose
function is to phosphorylate other proteins, and
(2) the activity of this enzyme is controlled by a protein whose
concentration varies from one stage of the cell cycle to another
Fluctuation of cyclin and MPF levels during the

cell cycle
MPF performs several functions to control cell cycle.
1. MPF function either directly as a kinases or indirectly by activating other

kinases.
Ex. MPF causes phosphorylation of other proteins of nuclear lamina-which

promotes fragmentation of the nuclear envelop during prometaphase of
mitosis.
2. MPF also involved in the condensation of chromosomes and spindle

formation during prophase.
The MPF complexes add phosphate tags to several different proteins in
the nuclear envelope, resulting in its breakdown (a key event of early M
phase), and also activate targets that promote chromosome
condensation and other M phase events.
Cdk-cyclin complex called

MPF
To study genetic control of cell cycle two species of yeast cells were
used
Budding yeast, Fission yeast
Saccharomyces cerevisiae Schizosaccharomyces pombe
reproduces through the reproduces by elongating itself and then

formation of buds at one end of splitting into two equalsized cells
the cell.
Cdk found was cdc28 Cdk found was cdc2
At both the checkpoints G1 and G2 cdk
used is cdc 2 but involves attachment
with different cyclins.
Fission yeast contd.
First transition point called START, occurs in late G1 phase involves

activation of cdc2 by one or more G1/S cyclins, once START point clear,
cell will ultimately completes cell cycle.
Second checkpoint-Passage from G2 to mitosis requires activation of cdc2

by a different group of cyclins—the mitotic cyclins
Third checkpoint-middle of M-phase, which determines whether cell will

complete cell division and re-enter G1 of the next cycle.
Exit from mitosis and entry into G1 depends on a rapid decrease in Cdk
activity that results from a plunge in concentration of the mitotic cyclins
Model of cell cycle regulation in fission yeast
START G2-M transition 3 checkpoint-

1 checkpoint 2 checkpoint sharp decline in
mitotic cyclins
Checkpoints are surveillance mechanisms that halt the progress of the cell
cycle if
(1) any of the chromosomal DNA is damaged, or

(2) certain critical processes, such as DNA replication during S phase or
chromosome alignment during M phase, have not been properly
completed.
Checkpoints ensure that each of the various events that make up the cell
cycle occurs accurately and in the proper order.
Damage to DNA also leads to the synthesis of proteins that directly inhibit the
cyclin–Cdk complex that drives the cell cycle.
For example, cells exposed to ionizing radiation in G1 synthesize a protein called

p21 (molecular mass of 21 kDa) that inhibits the kinase activity of the G1 Cdk.
This prevents the cells from phosphorylating key substrates and from entering S
phase.
p53 involvement in control of cell growth
p53 is normally very short-lived, but its phosphorylation by Chk2 (other checkpoint
kinase called Chk2) stabilizes the protein, enhancing its ability to activate p21
transcription. p21 once transcribed and translated it directly inhibits the Cdk.
Cdk Inhibitors Cdk activity can be blocked by a variety of inhibitors. In budding yeast, for
example, a protein called Sic1 acts as a Cdk inhibitor during G1.
The degradation of Sic1 allows the cyclin–Cdk that is present in the cell to initiate DNA
replication.
P
(p21)
Functions of Meiosis
1. Production of haploid (n) gametes: so, that fertilization restores the

normal somatic (2n) chromosome number.
2. Production of tremendous amounts of genetic variation.
3. Segregation of the two alleles of each gene. This take place due to
pairing between the two homologues of each chromosome and their
separation at the first anaphase.
4. Recombination between linked genes due to crossing over during
pachytene stage.
5. Meiosis facilitates segregation and independent assortment of
chromosomes and genes.
6. In sexually reproducing species, meiosis is essential for the continuity
of generation. Because meiosis results in the formation of male and
female gametes and union of such gametes leads to the development
of zygotes and thereby new individual.

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Cell cycle control system

Cell cycle is regulated by checkpoints by both internal and external controls.

If a cell receives a go-ahead signal at G1 check point, it will usually completes

This include regulatory proteins, which are of two types:

• Protein kinases are enzymes that activate or inactivate other proteins

• For their activation, they attached with cyclin.

So, MPF consists of two subunits

Cyclin Regulatory subunit

Fluctuation of cyclin and MPF levels during the

1. MPF function either directly as a kinases or indirectly by activating other

Ex. MPF causes phosphorylation of other proteins of nuclear lamina-which

2. MPF also involved in the condensation of chromosomes and spindle

Cdk-cyclin complex called

Saccharomyces cerevisiae Schizosaccharomyces pombe

reproduces through the reproduces by elongating itself and then

First transition point called START, occurs in late G1 phase involves

Second checkpoint-Passage from G2 to mitosis requires activation of cdc2

Third checkpoint-middle of M-phase, which determines whether cell will

START G2-M transition 3 checkpoint-

(1) any of the chromosomal DNA is damaged, or

For example, cells exposed to ionizing radiation in G1 synthesize a protein called

p53 involvement in control of cell growth

1. Production of haploid (n) gametes: so, that fertilization restores the

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