CRISPR knockout genome-wide screens identify the HELQ-RAD52 axis in regulating the repair of cisplatin-induced single stranded DNA gaps.

ABSTRACT: Treatment with genotoxic agents, such as platinum compounds, is still the mainstay therapeutical approach for the majority of cancers. Our understanding of the mechanisms of action of these drugs is however imperfect, and continuously evolving. Recent advances in the field highlighted single stranded DNA (ssDNA) gap accumulation as a potential determinant underlying cisplatin chemosensitivity, at least in some genetic backgrounds, such as BRCA mutations. Cisplatin-induced ssDNA gaps form upon the arrest of replication forks at sites of cisplatin adducts, and restart of DNA synthesis downstream of the lesion through repriming catalyzed by the PRIMPOL enzyme. Here, we show that PRIMPOL overexpression in otherwise wildtype cells results in accumulation of cisplatin-induced ssDNA gaps without

SUBMITTER: Pale LM 

PROVIDER: S-EPMC11042333 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature