Sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition identifies ubiquitin-specific peptidase 11 (USP11) as a regulator of DNA double-strand break repair.

ABSTRACT: DNA damage repair and checkpoint responses prevent genome instability and provide a barrier to the development of cancer. Inherited mutations in DNA damage response (DDR) genes such as those that encode the homologous recombination (HR) proteins BRCA1 and BRCA2 cause cancer predisposition syndromes. PARP inhibitors are an exciting new class of targeted therapy for treating patients with HR repair-defective tumors. In this study, we use an RNAi screen to identify genes that when silenced cause synthetic lethality with the PARP inhibitor AZD2281. This screen identified the deubiquitylating enzyme USP11 as a participant in HR repair of DNA double-strand breaks. Silencing USP11 with siRNA leads to spontaneous DDR activation in otherwise undamaged cells and hypersensitivity to PARP inhibition,

SUBMITTER: Wiltshire TD 

PROVIDER: S-EPMC2863164 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature