What are the roles of p53 and p21 in this checkpoint?

If the DNA cannot be repaired, p53 can trigger apoptosis, or cell suicide, to prevent the duplication of damaged chromosomes. As p53 levels rise, the production of p21 is triggered. p21 enforces the halt in the cycle dictated by p53 by binding to and inhibiting the activity of the Cdk/cyclin complexes.

What CDK p21 inhibits?

p21 binds and inhibits cyclin-CDK2, cyclin-CDK1, and cyclin-CDK4,6 complexes and thus, inhibits cell cycle progression during G1 and S phases [10,11].

Which cell cycle checkpoint is disrupted by problems with p53?

Cells in which p53 is deleted or mutated lose the G1 checkpoint and no longer arrest at the G1/S transition. Although they maintain a G2 arrest, this arrest can decay over time thus allowing cells to enter mitosis with unrepaired DNA damage and mutations that increase the risk of progression to malignancy.

What happens if p21 is mutated?

The p21 gene, a downstream effector of the p53 tumor suppressor gene is involved in breast carcinogenesis and in other malignancies. The mutational and hypermethylation profile of the p21 gene in the north Indian population revealed that they are associated with breast cancer development and progression.

Does p53 inhibit CDK?

p53 levels rise, leading to accumulation of its transcriptional targets including p21/WAF1/CIP1, which binds to and inhibits CDKs and blocks progression through the cell cycle.

Can p21 expression be regulated independently of p53?

However, p21 expression can be regulated independently of p53, and here we show that expression of p21 in various tissues during development and in the adult mouse occurs … Expression of p21 has been shown to be up-regulated by the p53 tumor suppressor gene in vitro in response to DNA-damaging agents.

Is senescence in p53-defective tumor cells dependent on p21 up-regulation?

Chk2-dependent senescence occurred in p53-defective tumor cells and was dependent on p21 up-regulation, thus revealing a novel p53-independent mechanism leading to p21 accumulation and senescence.

What is the function of p21 in the cell cycle?

The p21 protein is not required for the immediate and transient p53-independent cell cycle arrests following checkpoint activation. However, its accumulation contributes to maintenance of the arrests at G 1 -S and G 2 -M through inhibition of the cyclin-dependent kinases that regulate these cell cycle transitions ( 11, 12 ).

How do p21 and p53-responsive genes respond to DNA damage?

Because modulation of p21 and various other genes in response to DNA damage is primarily a consequence of p53-dependent transcriptional regulation, we determined mRNA levels of several p53-responsive genes using quantification real-time reverse transcription-PCR.