Wss1 homolog from Candida albicans and its role in DNA-protein crosslink tolerance.

Abstract:

: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 (CaWss1) using bioinformatics, genetic complementation, and biochemical studies. We showed that CaWss1 promotes cell survival under genotoxic stress conditions that generate DPCs and that the catalytic metalloprotease domain of CaWss1 is essential for its cellular function. Interactions of CaWss1 with Cdc48 and small ubiquitin-like modifier, although not strictly required, contribute to the function of CaWss1 in the suppression of the growth defects under DPC-inducing conditions. This report is the first investigation of the role of CaWss1 in DPC tolerance in C. albicans.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Homchan A,Sukted J,Mongkolsuk S,Jeruzalmi D,Matangkasombut O,Pakotiprapha D

doi

10.1111/mmi.14518

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

409-422

issue

3

eissn

0950-382X

issn

1365-2958

journal_volume

114

pub_type

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