Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks.

ABSTRACT: Hexavalent chromium [Cr(VI)] damages DNA and causes cancer, but it is unclear which DNA damage responses (DDRs) most critically protect cells from chromate toxicity. Here, genome-wide quantitative functional profiling, DDR measurements and genetic interaction assays in Schizosaccharomyces pombe reveal a chromate toxicogenomic profile that closely resembles the cancer chemotherapeutic drug camptothecin (CPT), which traps Topoisomerase 1 (Top1)-DNA covalent complex (Top1cc) at the 3' end of single-stand breaks (SSBs), resulting in replication fork collapse. ATR/Rad3-dependent checkpoints that detect stalled and collapsed replication forks are crucial in Cr(VI)-treated cells, as is Mus81-dependent sister chromatid recombination (SCR) that repairs single-ended double-strand breaks (seDSBs) at

SUBMITTER: Ganguly A 

PROVIDER: S-EPMC6128646 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature