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Wss1 homolog from Candida albicans and its role in DNA–protein crosslink tolerance
Author(s) -
Homchan Aimorn,
Sukted Juthamas,
Mongkolsuk Skorn,
Jeruzalmi David,
Matangkasombut Oranart,
Pakotiprapha Danaya
Publication year - 2020
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14518
Subject(s) - biology , candida albicans , corpus albicans , dna damage , dna replication , dna repair , dna , systemic candidiasis , genetics , microbiology and biotechnology , immune system
Candida albicans is an opportunistic yeast that can cause life‐threatening systemic infection in immunocompromised individuals. During infections, C. albicans has to cope with genotoxic stresses generated by the host immune system. DNA–protein crosslink (DPC), the covalent linkage of proteins with DNA, is one type of DNA damages that can be caused by the host immune response. DPCs are bulky lesions that interfere with the progression of replication and transcription machineries, and hence threaten genomic integrity. Accordingly, either a DPC tolerance mechanism or a DPC repair pathway is essential for C. albicans to maintain genomic stability and survive in the host. Here, we identified Wss1 (weak suppressor of Smt3) in C. albicans ( Ca Wss1) using bioinformatics, genetic complementation, and biochemical studies. We showed that Ca Wss1 promotes cell survival under genotoxic stress conditions that generate DPCs and that the catalytic metalloprotease domain of Ca Wss1 is essential for its cellular function. Interactions of Ca Wss1 with Cdc48 and small ubiquitin‐like modifier, although not strictly required, contribute to the function of Ca Wss1 in the suppression of the growth defects under DPC‐inducing conditions. This report is the first investigation of the role of Ca Wss1 in DPC tolerance in C. albicans .