USP1 in regulation of DNA repair pathways

Ubiquitin-specific protease 1 (USP1) is the founding member of the family of cysteine proteases that catalyse hydrolysis of the isopeptide bond between ubiquitin and targets. USP1 is often overexpressed in various cancers, and expression levels correlate with poor prognosis. USP1 and its partner USP1-associated Factor 1 (UAF1) are required for deubiquitinating monoubiquitin signals in DNA interstrand crosslink repair, and in Translesion synthesis, among others, and both proteins are subject to multiple regulations themselves. This review covers recent findings on the mechanisms and functions of USP1 in DNA repair, its regulation, and its potential as a target for therapeutic intervention. • USP1 structure and function. • Role of USP1 deubiquitination in DNA repair pathways. • Potential druggability of USP1. • Regulation of USP1 activity.