RAD52 and ERCC6L/PICH have a compensatory relationship for genome stability in mitosis

• DOI: 10.1371/journal.pgen.1011479
• Publication Date: 2024-11-19T18:38:24Z
• Authors: Beth Osia; Arianna Merkell; Felicia Wednesday...; Xiaoli Ping; Jeremy M. Stark
• Keywords: RAD52; Prometaphase; Interphase

Mammalian RAD52 is a DNA repair factor with strand annealing and recombination mediator activities that appear important in both interphase mitotic cells. Nonetheless, dispensable for cell viability. To query synthetic lethal relationships, we performed genome-wide CRISPR knock-out screens identified hundreds of candidate interactions. We then secondary screening genes which depletion causes reduced viability elevated genome instability (increased 53BP1 nuclear foci) RAD52-deficient One such was ERCC6L, marks bridges during anaphase, hence stability mitosis. Thus, investigated the functional interrelationship between ERCC6L. found deficiency increases ERCC6L-coated anaphase ultrafine bridges, ERCC6L foci prometaphase These effects were enhanced replication stress (i.e. hydroxyurea) topoisomerase IIα inhibition (ICRF-193), where post-treatment effect timings consistent defects addressing Altogether, suggest co-compensate to protect