Cohesin still drives homologous recombination repair of DNA double-strand breaks in late mitosis

Abstract

The cohesin complex maintains sister chromatid cohesion from S phase to anaphase onset. Cohesin also plays roles in chromosome structure and DNA repair. At anaphase onset, the cohesin subunit Scc1 is cleaved to allow segregation in an orderly manner, although some residual cohesin subunits remain to maintain chromosome structure. Efficient DNA double-strand break (DSB) repair by homologous recombination (HR) with the sister chromatid also depends on cohesin. Here, we have tested whether residual cohesin is important during DSB repair in anaphase/telophase (late mitosis). Using the well-established MAT switching system, we first show that HR is molecularly functional in late mitosis, and then show that cohesin is required for its efficiency. During DSBs in late mitosis, the segregated sister loci get closer and have episodes of coalescence, which may favour repair by HR. Here, we also show that these cytological phenotypes also depend on cohesin. Finally, full-length Scc1 returns after DSBs in late mitosis, suggesting thatde novowidespread cohesin complexes can support these retrograde behaviours.

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

“…To check whether this increase was due to a deficiency in DDC shutdown in Δ msc1 , we repeated the DSB generation by HO induction, but washed out β-estradiol after 1h, thus allowing late-M cells to recover from the DSB insult. HO is known to be rather unstable and is rapidly degraded once the HO promoter is silenced 26–28 . Rad53 remained hyperphosphorylated for the first 3 h after recovery and was gradually dephosphorylated over the next 6 h (Fig S5).…”

“…In G2/M, the HO DSB is efficiently repaired through HR 16,17 . Importantly, the HO DSB is also repaired by HR in late mitosis 28 . To determine whether Msc1 impinges on the overall repair of the HO DSB, we compared the WT and the Δ msc1 strains (Fig 3B,C).…”