Emerging roles of Wss1 in the survival of Candida albicans under genotoxic stresses
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MINI-REVIEW
Emerging roles of Wss1 in the survival of Candida albicans under genotoxic stresses Aimorn Homchan1 · Juthamas Sukted2 · Oranart Matangkasombut3,4 · Danaya Pakotiprapha1 Received: 29 September 2020 / Revised: 19 October 2020 / Accepted: 20 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Wss1 · Candida albicans · DNA −protein crosslink repair · SUMO processing
Introduction Candida albicans is a commensal organism that can become an opportunistic pathogen and cause systemic infections with a high mortality rate in human, particularly in Communicated by M. Kupiec. Aimorn Homchan and Juthamas Sukted contributed equally to this work. * Oranart Matangkasombut [email protected] * Danaya Pakotiprapha [email protected] 1
Department of Biochemistry and Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
2
Applied Biological Sciences Program, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand
3
Laboratory of Biotechnology, Chulabhorn Research Institute, Bangkok 10210, Thailand
4
Department of Microbiology and Research Unit on Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand
immunocompromised patients. Successful colonization and infection depend on the ability of C. albicans to survive and grow in the host, whose immune cells generate genotoxic stresses against invading pathogens. These stresses can trigger DNA damages, including DNA strand breaks, DNA strand crosslinks, as well as DNA − protein crosslinks (Cadet and Wagner 2013; Giglia-Mari et al. 2011; Tretyakova et al. 2015). To survive under these stresses and maintain its genomic integrity, C. albicans relies on DNA repair pathways, several of which have been extensively studied and shown to be required for virulence and survival in the host (Andaluz et al. 2001; Chauhan et al. 2005). However, the
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