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

The repair of DNA double-strand breaks by recombination requires the presen ce of an undamaged copy that is used as a template during the repair proces s. Because cells acquire resistance to gamma irradiation during DNA replica tion [1] and because sister chromatids are the preferred partner for double -strand break repair in mitotic diploid yeast cells [2], it has long been s uspected that cohesion between sister chromatids might be crucial for effic ient repair. This hypothesis is consistent with the sensitivity to gamma ir radiation of mutants defective in the cohesin complex [3] that holds sister chromatids together from DNA replication until the onset of anaphase (revi ewed in [4-6]), It is also in accordance with the finding that surveillance mechanisms (checkpoints) that sense DNA damage arrest cell cycle progressi on in yeast by causing stabilization of the securin Pds1, thereby blocking sister chromatid separation [7-10]. 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 thr ough S phase in the presence of cohesin, and not cohesin per se, is essenti al for efficient double-strand break repair during G2 in yeast. Proteins ne eded to load cohesin onto chromosomes (Scc2) [11-13] and to generate cohesi on during S phase (Ecol) [14, 15] are also shown to be required for repair. Our results confirm what has long been suspected but never proven, that co hesion between sister chromatids is essential for efficient double-strand b reak repair in mitotic cells. (C) 2001 Elsevier Science Ltd. All rights res erved.