DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression.

ABSTRACT: Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4^Cdt2 and SCF^Skp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable swi

SUBMITTER: Barr AR 

PROVIDER: S-EPMC5364389 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature