Msc1 is a nuclear envelope protein that reinforces DNA repair in late mitosis

Abstract

Precise double -strand break (DSB) repair is a paramount for genome stability. Homologous recombination (HR) repairs DSBs when cyclin-dependent kinase (CDK) activity is high, which correlates with the availability of the sister chromatid as a template. However, anaphase and telophase are paradoxical scenarios since high CDK favors HR despite sister chromatids being no longer aligned. To identify factors specifically involved in DSB repair in late mitosis, we have undertaken comparative proteomics in Saccharomyces cerevisiae and found that meiotic sister chromatid 1 (Msc1), a poorly characterized nuclear envelope protein, is significantly enriched upon both random and guided DSBs. We further show that D msc1 is more sensitive to DSBs in late mitosis, and has a delayed repair of DBSs, as indicated by increased Rad53 hyperphosphorylation, a higher presence of RPA foci, fewer Rad52 repair factories, and slower HR completion. We propose that Msc1 favors the later stages of HR and the timely completion of DSB repair before cytokinesis.