| Summary: | Fun30, an ATP-dependent chromatin remodeler from <i>S. cerevisiae</i>, is known to mediate both regulation of gene expression as well as DNA damage response/repair. The Fun30 from <i>C. albicans</i> has not yet been elucidated. We show that <i>C. albicans</i> Fun30 is functionally homologous to both <i>S. cerevisiae</i> Fun30 and human SMARCAD1. Further, <i>C. albicans</i> Fun30 can mediate double-strand break end resection as well as regulate gene expression. This protein regulates transcription of <i>RTT109</i>, <i>TEL1</i>, <i>MEC1</i>, and <i>SNF2</i>-genes that encode for proteins involved in DNA damage response and repair pathways. The regulation mediated by <i>C. albicans</i> Fun30 is dependent on its ATPase activity. The expression of <i>FUN30</i>, in turn, is regulated by histone H3K56 acetylation catalyzed by Rtt109 and encoded by <i>RTT109</i>. The <i>RTT109Hz</i>/<i>FUN30Hz</i> 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 <i>MEC1</i>, <i>RAD9</i>, <i>MRC1</i>, and <i>RAD5</i> 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 <i>RAD9</i> is upregulated, which is modulated by both Fun30 and H3K56 acetylation. Thus, Fun30 and H3K56 acetylation mediate the response to genotoxic agents in <i>C. albicans</i> by regulating the expression of DNA damage response and repair pathway genes.
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