Homologous Recombination-dependent Rescue of Deficiency in the Structural Maintenance of Chromosomes (Smc) 5/6 Complex

摘要: The essential and evolutionarily conserved Smc5-Smc6 complex (Smc5/6) is critical for the maintenance of genome stability. Partial loss Smc5/6 function yields several defects in DNA repair, which are rescued by inactivation homologous recombination (HR) machinery. Thus HR thought to be toxic cells with defective Smc5/6. Recent work has highlighted a role Sgs1 helicase preventing accumulation unresolved intermediates. Here we investigate how deletion MPH1, encoding orthologue human FANCM helicase, rescues damage sensitivity smc5/6 but not sgs1Δ mutants. We find that MPH1 diminishes intermediates within both cells, suggesting sufficient decrease use template switch (TSR) bypass lesions. further explain avoidance TSR nonetheless insufficient rescue mutants, demonstrating requirement Sgs1, along post-replicative repair (PRR) machinery, pathway operates mph1Δ In addition, map region Mph1 binds Smc5, describe novel allele protein unable bind Smc5 (mph1-Δ60). Remarkably, mph1-Δ60 supports normal growth responses damaging agents, indicating does simply restrain recombinogenic activity via direct binding. These data as whole highlight resolution Mph1-dependent