1 Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, China.
2 Biology Department, Concordia University, Montreal, QC H4B 1R6, Canada.
3 Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642.

Hof1 plays a checkpoint related role in MMS induced DNA damage response in Candida albicans.

Mol Biol Cell. 2020 Jan 15;:mbcE19060316

Authors: Feng J, Islam A, Bean B, Feng J, Sparapani S, Shrivastava M, Goyal A, Omran RP, Mallick J, Whiteway M

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 Candida albicans, a subset of genes involved in the response to DNA damage-induced genome instability and morphological changes have been found to regulate virulence. To better understand the virulence-linked DNA repair network, we screened for MMS sensitivity within the GRACE conditional expression collection and identified 56 hits. One of these potential DNA damage repair-associated genes, a HOF1 conditional mutant, unexpectedly had a previously characterized function in cytokinesis. Deletion of HOF1 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 downregulated in a Rad53-dependent manner and its importance in the MMS response is reduced when Rad53 is overexpressed or when RAD4 or RAD23 are deleted. Together, this work expands our understanding of the C. albicans DNA repair network and uncovers interplay between the cytokinesis regulator Hof1 and the Rad53-mediated checkpoint.

PMID: 31940254 [PubMed - as supplied by publisher]