TAOK1 promotes filament formation in HR repair through phosphorylating USP7.

ABSTRACT: Poly-ADP-ribose polymerase (PARP) inhibitors are vital therapeutic agents that exploit synthetic lethality, particularly effective in tumors with homologous recombination (HR) defects. However, broadening their clinical utility remains a significant challenge. In this study, we conducted a high-throughput kinase inhibitor screen to identify potential targets exhibiting synthetical lethality with PARP inhibitors. Our results show that thousand and one amino acid protein kinase 1 (TAOK1) plays a pivotal role in the DNA damage response by phosphorylating ubiquitin specific peptidase 7 (USP7), thereby promoting its enzymatic activity and preventing the ubiquitylation and subsequent degradation of RAD51, a crucial protein in the filament formation of HR repair. Notably, genetic depletion or pha

SUBMITTER: Zhu TC 

PROVIDER: S-EPMC11962436 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature