OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1^S824.

ABSTRACT: Appropriate repair of damaged DNA and the suppression of DNA damage responses at telomeres are essential to preserve genome stability. DNA damage response (DDR) signaling consists of cascades of kinase-driven phosphorylation events, fine-tuned by proteolytic and regulatory ubiquitination. It is not fully understood how crosstalk between these two major classes of post-translational modifications impact DNA repair at deprotected telomeres. Hence, we performed a functional genetic screen to search for ubiquitin system factors that promote KAP1^S824 phosphorylation, a robust DDR marker at deprotected telomeres. We identified that the OTU family deubiquitinase (DUB) OTUD5 promotes KAP1^S824 phosphorylation by facilitating ATM activation, through stabilization of the ubiquit

SUBMITTER: Lam SY 

PROVIDER: S-EPMC11486905 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature