Msc1 is a nuclear envelope protein that reinforces DNA repair in late mitosis : [Preprint]

Precise double-strand break (DSB) repair is 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 Msc1, a poorly characterized nuclear envelope protein, is significantly enriched upon both random and guided DSBs. We further show that Δmsc1 is more sensitive to DSBs in late mitosis, and has a delayed repair of DBSs, as indicated by increased Rad53 hyperphosphorylation, fewer Rad52 repair factories, and slower HR completion. We discuss how Msc1 may favor the formation of Rad52 factories and the timely completion of HR before cytokinesis.