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Wss1 在白念珠菌应对遗传毒性应激中的生存中的新兴作用。

Emerging roles of Wss1 in the survival of Candida albicans under genotoxic stresses.

机构信息

Department of Biochemistry and Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Applied Biological Sciences Program, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, 10210, Thailand.

出版信息

Curr Genet. 2021 Feb;67(1):99-105. doi: 10.1007/s00294-020-01123-6. Epub 2020 Nov 2.

Abstract

This perspective aims to discuss the potential physiological roles and regulation mechanisms of the recently identified Candida albicans Wss1 protease important in DNA-protein crosslink (DPC) tolerance and repair. DPC is a bulky DNA lesion that blocks essential DNA transactions; thus, it poses a significant threat to genome integrity if left unrepaired. Discoveries of Wss1 in Saccharomyces cerevisiae and SPRTN in human as DPC proteases have demonstrated the importance of protease function in DPC repair. Our recent study revealed that Wss1 in C. albicans, an opportunistic pathogen that can cause life-threatening infection in immunocompromised individuals, also promotes DPC tolerance similarly to both S. cerevisiae Wss1 and human SPRTN. However, its molecular mechanism and regulation are still poorly understood. Here, we briefly discuss the recent insights into C. albicans Wss1 based on the information from S. cerevisiae, as well as outline the aspect of this protein that could make it a potential target for antifungal drug development.

摘要

本文旨在探讨最近发现的白念珠菌 Wss1 蛋白酶在 DNA-蛋白质交联 (DPC) 耐受和修复中的潜在生理作用和调控机制。DPC 是一种体积较大的 DNA 损伤,会阻碍关键的 DNA 交易;因此,如果不进行修复,它会对基因组完整性构成重大威胁。在酿酒酵母中发现 Wss1 和在人类中发现 SPRTN 作为 DPC 蛋白酶,都证明了蛋白酶在 DPC 修复中的重要性。我们最近的研究表明,白念珠菌中的 Wss1(一种机会性病原体,可在免疫功能低下的个体中引起危及生命的感染)也能像酿酒酵母 Wss1 和人类 SPRTN 一样促进 DPC 耐受。然而,其分子机制和调控仍知之甚少。在这里,我们根据酿酒酵母的信息,简要讨论了白念珠菌 Wss1 的最新研究进展,并概述了该蛋白的一个方面,这可能使其成为抗真菌药物开发的潜在靶点。

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