CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions.

ABSTRACT: The observation that BRCA1- and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in homologous recombination¹. The cytotoxicity of PARP inhibitors depends on PARP trapping, the formation of non-covalent protein-DNA adducts composed of inhibited PARP1 bound to DNA lesions of unclear origins^1-4. To address the nature of such lesions and the cellular consequences of PARP trapping, we undertook three CRISPR (clustered regularly interspersed palindromic repeats) screens to identify genes and pathways that mediate cellular resistance to olaparib, a clinically approved PARP inhibitor¹. Here we present a high-confidence set of 73 g

SUBMITTER: Zimmermann M 

PROVIDER: S-EPMC6071917 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature