Cdk2 strengthens the intra-S checkpoint and counteracts cell cycle exit induced by DNA damage.

ABSTRACT: Although cyclin-dependent kinase 2 (Cdk2) controls the G1/S transition and promotes DNA replication, it is dispensable for cell cycle progression due to redundancy with Cdk1. Yet Cdk2 also has non-redundant functions that can be revealed in certain genetic backgrounds and it was reported to promote the G2/M DNA damage response checkpoint in TP53 (p53)-deficient cancer cells. However, in p53-proficient cells subjected to DNA damage, Cdk2 is inactivated by the CDK inhibitor p21. We therefore investigated whether Cdk2 differentially affects checkpoint responses in p53-proficient and deficient cell lines. We show that, independently of p53 status, Cdk2 stimulates the ATR/Chk1 pathway and is required for an efficient DNA replication checkpoint response. In contrast, Cdk2 is not required for a s

SUBMITTER: Bacevic K 

PROVIDER: S-EPMC5647392 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature