PCNA dependent cellular activities tolerate dramatic perturbations in PCNA client interactions.

ABSTRACT: Proliferating cell nuclear antigen (PCNA) is an essential cofactor for DNA replication and repair, recruiting multiple proteins to their sites of action. We examined the effects of the PCNA^S228I mutation that causes PCNA-associated DNA repair disorder (PARD). Cells from individuals affected by PARD are sensitive to the PCNA inhibitors T3 and T2AA, showing that the S228I mutation has consequences for undamaged cells. Analysis of the binding between PCNA and PCNA-interacting proteins (PIPs) shows that the S228I change dramatically impairs the majority of these interactions, including that of Cdt1, DNMT1, PolD3^p66 and PolD4^p12. In contrast p21 largely retains the ability to bind PCNA^S228I. This property is conferred by the p21 PIP box sequence itsel

SUBMITTER: Wilson RH 

PROVIDER: S-EPMC5264654 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature