VPP 211: General Veterinary Pathology (1+1)

CELL CYCLE AND CYCLINS

Proliferationof cells are important in degeneration and repair and also a feature in neoplasia. The dividing cells undergo cyclical change i.e cell cycle and it has four phases.

• Presynthetic growth phase or G1 phase – this is thetime gap between end of mitosis and start of DNA synthesis.
• Synthetic phase or S phase – this is period of DNA synthesis and beginning of mitosis.
• A premitotic growth phase or G2 phase
• Mitotic phase or M phase
• A cell takes16 hours to give rise to another cell.

The time taken by different phases is as follows

Phases	Time taken (hours)
G1	5
S	7
G2	3
M	1

• The cell is usually in interphase and G1 is most variable period. G0 state wherein cell proliferation is arrested.
• The cyclins synthesized during specific phase of cell cycle are involved in activating cyclin dependant kinases (CDK).
• Once the job is completed, the cyclins leave their activity. This is the way the cell cycle or proliferation is regulated.
• G1 to S phase is regulated by cyclin D/CDK4, cyclin D/CDK6, cyclin D/CDK2.
• S phase is regulated by cyclin D/CDK2, cyclin A/CDK1.
• G2 to M phase transistion is regulated by cyclin B/CDK1.
• Cyclin D gene sare overexprssed in many cancers so that neoplastic transformation occurs. e.g.hepatic tumour, breast cancer.
• Cell cycle is also regulated by CDK inhibitors. e.g. CDKNIA (p21), p27 and p57. The members acting on cyclin D/CDK4 and cyclin D/CDK6 are p15, CDKN2A (p16), p18 and p19.

Cell cycle checkpoints

• Cell cycle checkpoints are used by the cell to monitor and regulate the progress of the cell cycle. Checkpoints prevent cell at specific points, allowing verification of necessary phase processes and repair of DNA damage. The cell cannot proceed to the next phase until checkpoint requirements have been met. The checkpoints are designed to ensure that damaged or incomplete DNA is not passed on to daughter cells. Two main checkpoints are: the G1/S checkpoint and the G2/M checkpoint. G1/S transition is a rate-limiting step in the cell cycle and is also known as restriction point. An alternative model of the cell cycle response to DNA damage has also been proposed, known as the post replication checkpoint. p53 plays an important role in triggering the control mechanisms at both G1/S and G2/M checkpoints.