RSC Facilitates Rad59-Dependent Homologous Recombination between Sister Chromatids by Promoting Cohesin Loading at DNA Double-Strand Breaks

Abstract

Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes contribute to homologous DNA repair are unknown. Here we have systematically assessed the role of budding yeast RSC (remodel structure of chromatin), an abundant, ATP-dependent chromatin-remodeling complex, in the cellular response to spontaneous and induced DNA damage. RSC physically interacts with the recombination protein Rad59 and functions in homologous recombination. Multiple recombination assays revealed that RSC is uniquely required for recombination between sister chromatids by virtue of its ability to recruit cohesin at DNA breaks and thereby promoting sister chromatid cohesion. This study provides molecular insights into how chromatin remodeling contributes to DNA repair and maintenance of chromatin fidelity in the face of DNA damage.

View publisher note:

Roles of RSC, Rad59, and Cohesin in Double-Strand Break Repair

ACKNOWLEDGMENTS

We thank the members of the S.E.L., P.S., A.M., and G.I. laboratories for helpful comments; K. J. Myung for sharing strains and discussions; and B. J. Daniel for FACS support.

This work was funded by grants from the NIH to S.E.L. (GM071011, 3R01 GM071011), P.S. (R01GM57814), A.M. (GM084242-01), and G.I. (GM080600 and 3R01GM080600). S.E.L. is a scholar of the Leukemia and Lymphoma Society.