Cell cycle

Cell cycle

• Cell cycle checkpoints are control mechanisms that ensure the fidelity of cell division in eukaryotic cells

• Consist several checkpoints – verify whether the processes at each phase of

the cell cycle have been accurately completed before progression into the next phase.

Function of cell cycle

• DNA damage be detected by sensor mechanisms

• When damage is found checkpoint uses a signal mechanism to target the cell for destruction via apoptosis

Definition

• The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to 1. doubling of its genome (DNA) in S phase (synthesis phase) of the cell cycle2. division and replication that produces two daughter cell.

Interphase

• G0

• G1

• S• G2

G0 phase

• The G0 phase (referred to the G zero phase) or resting phase is a period in the cell cycle in which cells exist in a quiescent state or senescent

• Either dormant or apoptosis• Red blood cell or neurons, become quiescent

when they reach maturity

• terminally differentiated cells• they do not need to divide ever again after

reach maturity• the cells leave G1 and enter an alternative

state called G0 where they stop dividing permanently

In relation to the cell cycle

• This usually occurs in response to a lack of growth factor or nutrients

• Or it already terminally differentiated• Until there is a reason for them to divide

Growth factor

• polypeptides that stimulate cell proliferation and maturation

• usually it is a protein or a steroid hormone• regulating a variety of cellular processes• Example– bone morphogenetic proteins stimulate bone cell

differentiation– fibroblast growth factors and vascular endothelial

growth factors stimulate angiogenesis.

Cont. G0

• Cyclin C• Cdk 3

G1 PHASE

G1 phase

• During G1 phase, the cell grows in size and synthesizes mRNA and protein

• Preparation for subsequent steps leading to mitosis.

• G1 phase ends when the cell moves into the S phase of interphase.

Cont. G1 phase

• major control switches for the cell cycle– G1 cyclins (D cyclins)

– G1 Cdk (Cdk4)- binds with cyclin

• Signal the cell to prepare the chromosome for replication

Cont. G1 phase

• If a cell is signaled to remain undivided, instead of moving onto the S phase, it will leave the G1 phase and move into a state of dormancy

• p27 is a protein that binds to cyclin and cdk –blocks entry into S phase if

• p53 is a protein that responsible to block the cell cycle if the DNA is damaged.

S PHASE

S phase

• Major event in S-phase is DNA replication• Create exactly two identical semi-conserved

chromosomes• Prevents more than one replication from

occurring

Cont. S-phase

• S-phase cyclins (cyclins E and A)• S-phase Cdk (Cdk2)• p53

G2 PHASE

G2 phase

• Start with cyclin E destroyed• G2 phase is a period of rapid cell growth

and protein synthesis during which the cell readies itself for mitosis

• G2 phase is not a necessary part of the cell cycle

• Some cancer proceed directly from DNA replication to mitosis.

Cont. G2 phase

• mitotic cyclins (B cyclins)• M-phase Cdk (Cdk1)

M-phase promoting factor

Cont. G2 phase

• M-phase promoting factor into the nucleus initiates– assembly of the mitotic spindle– breakdown of the nuclear envelope– cessation of all gene transcription– condensation of the chromosomes

M PHASE

Mitosis

• Process separates the chromosomes in its cell nuclues into two identical sets of chromosomes, followed immediately by cytokinesis

• Mitosis is the transferring of the parent cell's genome into two daughter cells

• Prophase, Metaphase, Anaphase, Telophase

Prophase

• Chromatin fibers become tightly coiled, condensing into discrete chromosomes

• Two sister chromatids, bound together at the centromere

• Visible at high magnification through a light microscope

• M-phase promoting factor

Prometaphase

• The nuclear membrane disintegrates and microtubules invade the nuclear space

• Late prometaphase, each chromosome forms two kinetochores at its centromere, one attached at each chromatid.

• M-phase promoting factor

Metaphase

• Two centrosomes start pulling the chromosomes through their attached centromeres towards the two ends of the cell

• Convene along the metaphase plate or equatorial plane

• This line is called the spindle equator• anaphase-promoting complex

Anaphase

• Entrance triggered by inactivation of M-phase promoting factor.

• First, the proteins that bind sister chromatids together are cleaved, become separate daughter chromosomes

• Then, the polar microtubules elongate, pulling the centrosomes

Cont. Anaphase

Anaphase-promoting complex1. allows the sister chromatids at the metaphase plate to

separate and move to the poles = anaphase– Cohesin breakdown is caused by

a protease called separase (also known as separin).– Separase is kept inactive until late metaphase by an

inhibitory chaperone called securin.– Anaphase begins when the anaphase promoting complex

(APC/C) destroys securin (by tagging it with ubiquitin for deposit in a proteasome) thus ending its inhibition of separase and allowing

– separase to break down cohesin.

Cont. Anaphase

2. destroys B cyclins. This is also done by attaching them to ubiquitin which targets them for destruction by proteasomes.

3. turns on synthesis of G1 cyclins (D) for the next turn of the cycle.

4. degrades geminin, a protein that has kept the freshly-synthesized DNA in S phase from being re-replicated before mitosis.

Telophase

• Two sets of daughter chromosome pulled completely apart

• Reversal of prophase and prometaphase events• Daughter chromosomes attach at opposite ends of the

cell. A new nuclear membrane, using the membrane vesicles of the parent cell's old nuclear membrane, forms around each set of separated daughter chromosomes

• The nucleoli reappear. Both sets of chromosomes, now surrounded by new nuclei, begin to "relax" or decondense back into chromatin

Cytokinesis

• Division is also driven by vesicles derived from the Golgi apparatus

• Each daughter cell has a complete copy of the genome of its parent cell. The end of cytokinesis marks the end of the M-phase.

Significance

• Development and growth• Cell replacement• Regeneration• Asexual reproduction

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