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.

中文翻译：

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来自白色念珠菌的Wss1同源物及其在DNA-蛋白质交联耐受中的作用。

白色念珠菌是一种机会酵母，可在免疫受损的个体中引起危及生命的全身感染。在感染期间，白色念珠菌必须应对宿主免疫系统产生的遗传毒性压力。DNA-蛋白质交联（DPC）是蛋白质与DNA的共价键，是宿主免疫反应可能引起的一种DNA损伤。DPC是体积庞大的病变，会干扰复制和转录机制的进程，从而威胁基因组完整性。因此，DPC耐受机制或DPC修复途径对于白色念珠菌维持基因组稳定性和在宿主中生存至关重要。在这里，我们确定了白色念珠菌中的Wss1（Smt3的弱抑制剂）（Ca Wss1）使用生物信息学，遗传互补和生化研究。我们发现，钙WSS1促进了产生毛乳头细胞基因毒性应激条件下和催化金属蛋白酶结构域细胞存活钙WSS1是其细胞功能是必不可少的。尽管没有严格要求，但Ca Wss1与Cdc48和小的泛素样修饰剂之间的相互作用有助于Ca Wss1在DPC诱导条件下抑制生长缺陷的功能。该报告是首次调查Ca Wss1在白色念珠菌对DPC耐受性中的作用。