Ontology highlight
ABSTRACT:
SUBMITTER: Lim KS
PROVIDER: S-EPMC6390489 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Lim Kah Suan KS Li Heng H Roberts Emma A EA Gaudiano Emily F EF Clairmont Connor C Sambel Larissa Alina LA Ponnienselvan Karthikeyan K Liu Jessica C JC Yang Chunyu C Kozono David D Parmar Kalindi K Yusufzai Timur T Zheng Ning N D'Andrea Alan D AD
Molecular cell 20181201 6
BRCA1-deficient tumor cells have defects in homologous-recombination repair and replication fork stability, resulting in PARP inhibitor sensitivity. Here, we demonstrate that a deubiquitinase, USP1, is upregulated in tumors with mutations in BRCA1. Knockdown or inhibition of USP1 resulted in replication fork destabilization and decreased viability of BRCA1-deficient cells, revealing a synthetic lethal relationship. USP1 binds to and is stimulated by fork DNA. A truncated form of USP1, lacking it ...[more]