Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in .

Fun30, an ATP-dependent chromatin remodeler from , is known to mediate both regulation of gene expression as well as DNA damage response/repair. The Fun30 from has not yet been elucidated. We show that Fun30 is functionally homologous to both Fun30 and human SMARCAD1. Further, Fun30 can mediate double-strand break end resection as well as regulate gene expression. This protein regulates transcription of , , , and -genes that encode for proteins involved in DNA damage response and repair pathways. The regulation mediated by Fun30 is dependent on its ATPase activity. The expression of , in turn, is regulated by histone H3K56 acetylation catalyzed by Rtt109 and encoded by . The / mutant strain shows sensitivity to oxidative stress and resistance to MMS as compared to the wild-type strain. Quantitative PCR showed that the sensitivity to oxidative stress results from downregulation of , , , and expression; ChIP experiments showed that Fun30 but not H3K56ac regulates the expression of these genes in response to oxidative stress. In contrast, upon treatment with MMS, the expression of is upregulated, which is modulated by both Fun30 and H3K56 acetylation. Thus, Fun30 and H3K56 acetylation mediate the response to genotoxic agents in by regulating the expression of DNA damage response and repair pathway genes.