Role of the checkpoint clamp in double-strand break repair

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): This will be the first study to exploit the newly discovered function of the checkpoint clamp in homologous recombination repair. We have previously established that ATM- dependent phosphorylation of the checkpoint clamp protein Rad9 governs DNA repair pathways to prevent genomic instability during unperturbed cell cycle. We recently learned that BRCA1 (breast and ovarian cancer type 1) interacts with Rad9. We also identified DNA2 nucleases as Rad9 interacting proteins, and the interaction is enhanced by DNA damage. Based on our preliminary results, we hypothesis that the checkpoint clamp is involved in the double-strand break-end resection process. If we can identify the precise function of the checkpoint clamp in homologous recombination, then we will be well on the way to understanding how the checkpoint clamp regulates repair/replication proteins in order to maintain genomic stability. Understanding of DNA repair regulation, in turn, will likely hold the key to understanding what keeps the genome stable.