What is the role of p53 at the G2 checkpoint?

p53 protects mammals from neoplasia by inducing apoptosis, DNA repair and cell cycle arrest in response to a variety of stresses. Part of the mechanism by which p53 blocks cells at the G2 checkpoint involves inhibition of Cdc2, the cyclin-dependent kinase required to enter mitosis.

Does p53 promote cell cycle arrest?

These data indicate that p53 can promote cell survival by inducing reversible cell cycle arrest, thereby allowing for DNA repair.

How does p53 help in cell regulation?

In normal cells, the p53 protein level is low. DNA damage and other stress signals may trigger the increase of p53 proteins, which have three major functions: growth arrest, DNA repair and apoptosis (cell death). The growth arrest stops the progression of cell cycle, preventing replication of damaged DNA.

What occurs during G2 phase of the cell cycle?

Gap 2 (G2): During the gap between DNA synthesis and mitosis, the cell will continue to grow and produce new proteins. Mitosis or M Phase: Cell growth and protein production stop at this stage in the cell cycle.

How is the G2 checkpoint controlled?

The G2 Checkpoint 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. If the DNA has been correctly replicated, cyclin dependent kinases (CDKs) signal the beginning of mitotic cell division.

Where does p53 stop the cell cycle?

The mechanism for this activity at the G1/S phase checkpoint is well understood, but its mechanism of action at the G2/M phase checkpoint remains to be elucidated. The p53 protein is thought to prevent chromosomal replication specifically during the cell cycle if DNA damage is present.

Why is p53 essential for the G2 transition?

Therefore, p53 is not required for the initial arrest of HCT116 cells in G2 but is essential for the long-term maintenance of the arrest. While it is possible that p53 also contributes to the initial arrest, it is clear that additional pathways can cause arrest when p53 is missing.

What happens when p53 is deleted in MEF cells?

In MEF cells, p53 deletion further compromises rather than rescues the proliferative potential of NS-depleted cells without changing their G2/M arrest fate before prophase entry.

How does p53 protect mammals from neoplasia?

p53 protects mammals from neoplasia by inducing apoptosis, DNA repair and cell cycle arrest in response to a variety of stresses. p53-dependent arrest of cells in the G1 phase of the cell cycle is an important component of the cellular response to stress.

How does NS loss lead to G2 / M arrest?

In cancer (HCT116) cells, NS loss leads to G2/M arrest under both p53wt and p53ko conditions and increases phosphorylated cdc2 more in p53ko than in p53wt cells, as it does in MEF cells.