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.

Iron-responsive Transcription Factor Aft1 Interacts with Kinetochore Protein Iml3 and Promotes Pericentromeric Cohesin

“…Indeed, histone modifications dependent on a functional kinetochore have been reported at the centromere, and these modifications contribute to chromosome segregation (42). Also, establishment of cohesion has been linked to numerous chromatin regulators and histone modifications (43)(44)(45)(46)(47), and chromatin-remodeling complexes were also found to interact with kinetochore proteins and localize to the centromere (13,48,49). Could Aft1 be recruiting such factors to the centromere?…”

Rad52/Rad59-dependent Recombination as a Means to Rectify Faulty Okazaki Fragment Processing

“…In addition, a subset of sister chromatid recombination (SCR) events, which is facilitated by the RSC chromatin-remodeling complex, also can occur independently of Rad51 (78,79). This Rad51-independent SCR pathway has been shown to require Rsc2 and Rsc7, which are the two critical components of the RSC chromatin-remodeling complex (79).…”

Phenotypic Consequences of a Spontaneous Loss of Heterozygosity in a Common Laboratory Strain of Candida albicans

“…Repair of MMS lesions involves pathways including base excision repair (Boiteux and Jinks-Robertson 2013), double strand break repair (Symington et al 2014), chromatin remodeling (Oum et al 2011) pathways, etc. Mutations in these genes will likely result in altered sensitivity to MMS.…”