Hof1 plays a checkpoint-related role in MMS-induced DNA damage response in <i>Candida albicans</i>

Abstract

Cells depend on robust DNA damage recognition and repair systems to maintain genomic integrity for survival in a mutagenic environment. In the pathogenic yeast <i>Candida albicans</i>, a subset of genes involved in the response to DNA damage-induced genome instability and morphological changes has been found to regulate virulence. To better understand the virulence-linked DNA repair network, we screened for methyl methane sulfonate (MMS) sensitivity within the GRACE conditional expression collection and identified 56 hits. One of these potential DNA damage repair-associated genes, a <i>HOF1</i> conditional mutant, unexpectedly had a previously characterized function in cytokinesis. Deletion of <i>HOF1</i> resulted in MMS sensitivity and genome instability, suggesting Hof1 acts in the DNA damage response. By probing genetic interactions with distinct DNA repair pathways, we found that Hof1 is genetically linked to the Rad53 pathway. Furthermore, Hof1 is down-regulated in a Rad53-dependent manner and its importance in the MMS response is reduced when Rad53 is overexpressed or when <i>RAD4</i> or <i>RAD23</i> is deleted. Together, this work expands our understanding of the <i>C. albicans</i> DNA repair network and uncovers interplay between the cytokinesis regulator Hof1 and the Rad53-mediated checkpoint.