Adel Alblihy, Reem Ali, Mashael Algethami, Alison A Ritchie, Ahmed Shoqafi, Shatha Alqahtani, Katia A Mesquita, Michael S Toss, Paloma Ordóñez-Morán, Jennie N Jeyapalan, Lodewijk Dekker, Martina Salerno, Edgar Hartsuiker, Anna M Grabowska, Emad A Rakha, Nigel P Mongan, Srinivasan Madhusudan
The MRE11 nuclease is essential during DNA damage recognition, homologous recombination, and replication. BRCA2 plays important roles during homologous recombination and replication. Here, we show that effecting an MRE11 blockade using a prototypical inhibitor (Mirin) induces synthetic lethality (SL) in BRCA2-deficient ovarian cancer cells, HeLa cells, and 3D spheroids compared to BRCA2-proficient controls. Increased cytotoxicity was associated with double-strand break accumulation, S-phase cell cycle arrest, and increased apoptosis...
June 30, 2023: International Journal of Molecular Sciences