Article
Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers.
Nucleic acids research - 22 May 2023
Patel Parasvi S, Algouneh Arash, Krishnan Rehna, Reynolds John J, Nixon Kevin C J, Hao Jun, Lee Jihoon, Feng Yue, Fozil Chehronai, Stanic Mia, Yerlici Talya, Su Peiran, Soares Fraser, Liedtke Elisabeth, Prive Gil, Baider Gary D, Pujana Miquel Angel, Mekhail Karim, He Housheng Hansen, Hakem Anne, Stewart Grant S, Hakem Razqallah
Abstract excerpt
BRCA1 mutations are associated with increased breast and ovarian cancer risk. BRCA1-mutant tumors are high-grade, recurrent, and often become resistant to standard therapies. Herein, we performed a targeted CRISPR-Cas9 screen and identified MEPCE, a methylphosphate capping enzyme, as a synthetic lethal interactor of BRCA1. Mechanistically, we demonstrate that depletion of MEPCE in a BRCA1-deficient setting led to...
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