Edgar Pinedo-Carpio, Julien Dessapt, Adèle Beneyton, Lauralicia Sacre, Marie-Anne Bérubé, Romain Villot, Elise G Lavoie, Yan Coulombe, Andréanne Blondeau, Jonathan Boulais, Abba Malina, Vincent M Luo, Anna-Maria Lazaratos, Jean-François Côté, Frédérick A Mallette, Alba Guarné, Jean-Yves Masson, Amélie Fradet-Turcotte, Alexandre Orthwein
Interstrand DNA cross-links (ICLs) represent complex lesions that compromise genomic stability. Several pathways have been involved in ICL repair, but the extent of factors involved in the resolution of ICL-induced DNA double-strand breaks (DSBs) remains poorly defined. Using CRISPR-based genomics, we identified FIGNL1 interacting regulator of recombination and mitosis (FIRRM) as a sensitizer of the ICL-inducing agent mafosfamide. Mechanistically, we showed that FIRRM, like its interactor Fidgetin like 1 (FIGNL1), contributes to the resolution of RAD51 foci at ICL-induced DSBs...
August 9, 2023: Science Advances