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 Introduction

The cell cycle is divided into

four major phases.
1. G-1 phase
2. S phase Interphase
3. G-2 phase

4. M phase Mitosis

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 G-1 Phase
First phase of Interphase

Cells synthesize RNAs ( transcription)

and proteins (Translation)

DNA replication machinery synthesized for

DNA replication (S phase preparation)

Chromosome remain uncondensed i.e. as

chromatin

Cell size increase

High metabolic activity for Transcription and In G1 phase cell is 2n

translation and chromatids is 2C

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 S Phase
Chromosome replicates during the S
(synthesis) phase. Diploid cells Haploid cells

Cell remain 2n even after DNA

synthesis because 2n denotes here
chromosomes number not amount of
DNA

Chromatid becomes 4C

Quantity of DNA (genome) doubles

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 G-2 Phase
Cell grows and prepare for Mitosis phase
No DNA synthesis occur
RNA and Protein synthesis continue
Mitotic cyclins expressed in inactive state that
may activate in M phase
Cyclins and CDK(cyclin dependent kinase) are
proteins that regulate the cell cycle
At the end of cell is ready to enter in M phase
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 M-Phase
Cell divide in this
phase
Comprise of 4 phase
and one cytokinesis
phase
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase
Cytokinesis
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 Control of the Cell Cycle
In 1970, a series of cell fusion
experiments carried out by Potu
Rao and Robert Johnson to
understand cell cycle regulation.

Rao and Johnson wanted to

know whether the cytoplasm of
cells contains regulatory factors
that affect cell cycle activities.

They approached the question 1. If a G1-phase and an M-phase cell were

by fusing mammalian cells that fused, the chromatin of the G1-phase nucleus
were in different stages of the underwent premature chromosomal
cell cycle. compaction suggesting that there were some
factors in M phase cell
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3. If S-phase fused with M phase cell
chromatin also became compacted. However,
replicating DNA is especially sensitive to
damage, so that compaction in the S-phase
nucleus led to the formation of pulverized
chromosomal fragments.
2. If G-2 phase and M- phase cell were
fused, the G2 chromosomes also underwent
premature chromosome compaction but not
like G1 phase because here DNA is doubled

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 Regulation of cell cycle
The factor that recognized by Rao & Johnson was MPF (maturation
promoting factors).

Entry of a cell into M phase is initiated by a protein

called maturation promoting factor (MPF ).

MPF composed of two subunits:

(1) A subunit with kinase activity that transfers
phosphate groups from ATP to specific serine and
threonine residues of specific
protein substrates and

(2) A regulatory subunit called cyclin. The term cyclin

was coined because the concentration of this
regulatory protein rises and falls in a predictable
pattern with each cell cycle

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 The cell cycle is controlled
primarily at two points, START and
the G2M transition.

Course of a cell through

these two critical points
necessitates the activation of the
same kinase (here cdc2)by
different classes of cyclins, either
G1/S or mitotic cyclins.

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 Cyclin-dependent kinases are often described as the engines that drive the
cell cycle through its various stages.
The activities of these enzymes are regulated by a variety of brakes and
accelerators that operate in combination with one another.

1. Cyclins can bind to the CDK and activate them making as an accelerator.

2. Phosphorylation or dephosphorylation can deactivate them working as a

Brakes

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 Cell cycle in Yeast

1. During G2, the cdc2 kinase interacts with a mitotic cyclin but remains inactive as the result of
phosphorylation of a key tyrosine residue (Tyr 15 in fission yeast) by Wee1.
2. A separate kinase, called CAK, transfers a phosphate to another residue (Thr 161), which is
required for cdc2 kinase activity later in the cell cycle.
3. When the cell reaches a critical size, an enzyme called Cdc25
phosphatase is activated, which removes the inhibitory phosphate on the
Tyr 15 residue. The resulting activation of the cdc2 kinase drives the cell
into mitosis.
4. By the end of mitosis (step 3), the stimulatory
phosphate group is removed from Thr 161 by another phosphatase. The
free cyclin is subsequently degraded, and the cell begins another cycle

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 Cell cycle in Mammalians
Unlike yeast cells, which have a single Cdk,mammalian cells produce
several different versions of this protein kinase.
Different cyclinCdk complexes target different groups of substrates at
different points within the cell cycle

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 Types of cyclins and its CDKs
G-1 Phase S Phase
Cyclin Ds+CDK4/6 Cyclin A+CDK2
1.Promote Preinitiation Cyclin E+CDK2
complex formation 1. DNA replication
2. Phosphorylation of pRB 2.G1 S transition

Cyclin+CDKs

Mitotic Phase
G-2 Phase Cyclin B+CDK1
Cyclin A/B+ CDK1 1. Mitotic spindle formation
1. Cytoskeleton disassembly 2.Degradation of Cyclin B lead to
G1 phase

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 Checkpoints: protecting from Cancer
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.

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