Subtle alterations in PCNA-partner interactions severely impair DNA replication and repair.

ABSTRACT: The robustness of complex biological processes in the face of environmental and genetic perturbations is a key biological trait. However, while robustness has been extensively studied, little is known regarding the fragility of biological processes. Here, we have examined the susceptibility of DNA replication and repair processes mediated by the proliferating cell nuclear antigen (PCNA). Using protein directed evolution, biochemical, and genetic approaches, we have generated and characterized PCNA mutants with increased affinity for several key partners of the PCNA-partner network. We found that increases in PCNA-partner interaction affinities led to severe in vivo phenotypic defects. Surprisingly, such defects are much more severe than those induced by complete abolishment of the respecti

SUBMITTER: Fridman Y 

PROVIDER: S-EPMC2953525 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature