Abundance of the RSC nucleosome‐remodeling complex is important for the cells to tolerate DNA damage in Saccharomyces cerevisiae

Abstract

The essential Nps1p/Sth1p is a catalytic subunit of the nucleosome-remodeling complex, RSC, of Saccharomyces cerevisiae that can alter nucleosome structure by using the energy of ATP hydrolysis. Besides the ATPase domain, Nps1p harbors the bromodomain, of which the function (s) have not yet been de¢ned. We have isolated a temperature-sensitive mutant allele of NPS1, nps1-13, which has amino acid substitutions within the bromodomain. This mutation perturbed the interaction between the RSC components and enhanced the sensitivity of the cells to several DNA-damaging treatments at the permissive temperature. Reduced expression of NPS1 also caused DNA damage sensitivity. These results suggest the importance of the Nps1p bromodomain in RSC integrity and a model in which high amounts of RSC would be required for the cells to overcome DNA damage.

ATP-Dependent Chromatin Remodeling and DNA Double-Strand Break Repair

“…Indeed, mutations in the Rsc1, Rsc2 and Sth1 subunits of the yeast RSC complex, a member of the SWI/SNF class of remodelers, render cells hypersensitive to DNA break-inducing agents. [14][15][16] As for INO80, mutations in RSC subunits did not lead to misregulation of DNA repair genes or defects in checkpoint activation, 14,17 implicating RSC directly in DNA repair. Moreover, like Ino80, the RSC subunit Rsc8 and the catalytic subunit Sth1, were shown to be recruited to an HO-induced DSB.…”

Chromatin disassembly and reassembly during DNA repair

“…RSC rsc1 and rsc2 Saccharomyces cerevisiae mutants are sensitive to gamma irradiation [40], and to radiomimetics, alkylating agents and UV when grown at their semipermissive temperatures [43][44][45]. SWI/SNF snf5 and snf2 Saccharomyces cerevisiae mutants are sensitive to radiomimetics and are moderately sensitive to alkylating agents and UV irradiation [45].…”

Chromatin modifications and DNA double-strand breaks: the current state of play

“…59 Again, it has been shown that mutations in the subunits of the Swi/Snf and RSC remodeling complexes result in hypersensitivity to agents that induce DSBs. [58][59][60][61] Overall, the role of chromatin remodelers in transcription (essentially their function in altering the topology of chromatin and increasing DNA accessibility) has predominantly been used as a basis to speculate on the function of these complexes in the DSB response pathway. Although intuitively this seems correct, further research is required to confidently assign specific roles for these chromatin-remodeling complexes in the context of DSB repair.…”