WRN helicase regulates the ATR-CHK1-induced S-phase checkpoint pathway in response to topoisomerase-I-DNA covalent complexes.

ABSTRACT: Checkpoints are cellular surveillance and signaling pathways that coordinate the response to DNA damage and replicative stress. Consequently, failure of cellular checkpoints increases susceptibility to DNA damage and can lead to profound genome instability. This study examines the role of a human RECQ helicase, WRN, in checkpoint activation in response to DNA damage. Mutations in WRN lead to genomic instability and the premature aging condition Werner syndrome. Here, the role of WRN in a DNA-damage-induced checkpoint was analyzed in U-2 OS (WRN wild type) and isogenic cells stably expressing WRN-targeted shRNA (WRN knockdown). The results of our studies suggest that WRN has a crucial role in inducing an S-phase checkpoint in cells exposed to the topoisomerase I inhibitor campthothecin (CPT

SUBMITTER: Patro BS 

PROVIDER: S-EPMC3244981 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature