High levels of RAD51 perturb DNA replication elongation and cause unscheduled origin firing due to impaired CHK1 activation.

ABSTRACT: In response to replication stress ATR signaling through CHK1 controls the intra-S checkpoint and is required for the maintenance of genomic integrity. Homologous recombination (HR) comprises a series of interrelated pathways that function in the repair of DNA double strand breaks and interstrand crosslinks. In addition, HR, with its key player RAD51, provides critical support for the recovery of stalled forks during replication. High levels of RAD51 are regularly found in various cancers, yet little is known about the effect of the increased RAD51 expression on intra-S checkpoint signaling. Here, we describe a role for RAD51 in driving genomic instability caused by impaired replication and intra-S mediated CHK1 signaling by studying an inducible RAD51 overexpression model as well as 10 bre

SUBMITTER: Parplys AC 

PROVIDER: S-EPMC4825602 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature