Sister chromatid cohesion is required for postreplicative double-strand break repair in Saccharomyces cerevisiae

Abstract

The repair of DNA double-strand breaks by recombination requires the presence of an undamaged copy that is used as a template during the repair process. Because cells acquire resistance to gamma irradiation during DNA replication and because sister chromatids are the preferred partner for double-strand break repair in mitotic diploid yeast cells, it has long been suspected that cohesion between sister chromatids might be crucial for efficient repair. This hypothesis is consistent with the sensitivity to gamma irradiation of mutants defective in the cohesin complex that holds sister chromatids together from DNA replication until the onset of anaphase (reviewed in) . It is also in accordance with the finding that surveillance mechanisms (checkpoints) that sense DNA damage arrest cell cycle progression in yeast by causing stabilization of the securin Pds1, thereby blocking sister chromatid separation. The hypersensitivity to irradiation of cohesin mutants could, however, be due to a more direct involvement of the cohesin complex in the process of DNA repair. We show here that passage through S phase in the presence of cohesin, and not cohesin per se, is essential for efficient double-strand break repair during G2 in yeast. Proteins needed to load cohesin onto chromosomes (Scc2) and to generate cohesion during S phase (Eco1) are also shown to be required for repair. Our results confirm what has long been suspected but never proven, that cohesion between sister chromatids is essential for efficient double-strand break repair in mitotic cells.

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

“…SMC1A is a protein involved in chromosome cohesion during cell division as well as in DNA repair. More precisely, SMC1A is related to the cohesion between sister chromatids during DNA replication and, at least in yeast, the cohesin complex also has functions in DNA repair and is essential for efficient double-strand break repair in mitotic cells (Sjögren and Nasmyth 2001).…”

A Second Proliferating Cell Nuclear Antigen Loader Complex, Ctf18-Replication Factor C, Stimulates DNA Polymerase η Activity

“…61). Interference studies of cohesin in various species demonstrate that cohesin functions not only in cohesion but also in DNA repair and recombination (62)(63)(64)(65). For example, the cohesin complex can be recruited to regions surrounding double strand breaks and can function in their repair (66 -68).…”

Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis

“…The hinge allows SMC proteins to fold back on themselves, forming an intramolecular coiled-coil and creating an ATPase by juxtaposing the Walker A and B domains (Haering et al, 2002). SMC proteins form stable heterodimers, most likely through interactions mediated by their hinge regions (Haering et al, 2002).Hypomorphic mutations of proteins in the SMC complexes render cells hypersensitive to genotoxic stress (Birkenbihl and Subramani, 1992;Lehmann et al, 1995;Sjogren and Nasmyth, 2001;Aono et al, 2002;Fujioka et al, 2002;Kim et al, 2002b;Yazdi et al, 2002;McDonald et al, 2003;Harvey et al, 2004). Cohesin may facilitate the homologous recombination repair of DSBs by holding sister-chromatids in proximity, promoting identification of an intact homologous duplex.…”