Hof1 plays a checkpoint-related role in MMS-induced DNA damage response in Candida albicans

Computational and Structural Biotechnology Journal

Islam

et al. 2020

Self Cite

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loss of Arp1, a putative actin-related protein, triggers filamentous and invasive growth and impairs pathogenicity in Candida albicans

Computational and Structural Biotechnology Journal

Islam

et al. 2020

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“…Similar to the pattern of ScRad53, the phosphorylated CaRad53 in C. albicans shows a slower gel migration, supplying an effective tool to study its phosphorylation status [35] , [36] . Nevertheless, according to current data, CaRAD53 is not essential in C. albicans, either the BWP17, SN148 or CEC3194 backgrounds [35] , [37] , [38] . Deleting CaRAD53 does, however, cause severe sensitivity to various genotoxic stresses, including MMS and HU [35] .…”

Section: Dna Damage Checkpoints In C Albicansmentioning

confidence: 66%

“…The base excision repair (BER) pathway repairs the damage that creates minor disturbances in the DNA helix [37] . This process is initiated by a series of glycosylases, including ScUng1, ScMag1, ScOgg1, ScNtg1, ScOgg2 and ScNtg2 in S. cerevisiae ( Table 1 ).…”

Section: Dna Damage Repair Pathways In C Albicansmentioning

confidence: 99%

DNA damage checkpoint and repair: From the budding yeast Saccharomyces cerevisiae to the pathogenic fungus Candida albicans

Computational and Structural Biotechnology Journal

Zhang

et al. 2021

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Cells are constantly challenged by internal or external genotoxic assaults, which may induce a high frequency of DNA lesions, leading to genome instability. Accumulation of damaged DNA is severe or even lethal to cells and can result in abnormal proliferation that can cause cancer in multicellular organisms, aging or cell death. Eukaryotic cells have evolved a comprehensive defence system termed the DNA damage response (DDR) to monitor and remove lesions in their DNA. The DDR has been extensively studied in the budding yeast Saccharomyces cerevisiae . Emerging evidence indicates that DDR genes in the pathogenic fungus Candida albicans show functional consistency with their orthologs in S. cerevisiae , but may act through distinct mechanisms. In particular, the DDR in C. albicans appears critical for resisting DNA damage stress induced by reactive oxygen species (ROS) produced from immune cells, and this plays a vital role in pathogenicity. Therefore, DDR genes could be considered as potential targets for clinical therapies. This review summarizes the identified DNA damage checkpoint and repair genes in C. albicans based on their orthologs in S. cerevisiae , and discusses their contribution to pathogenicity in C. albicans .

“…3A), suggesting a role of RAD23 independent from these genes in the UV response. In addition, a strain with a deletion of HOF1 (46) or PPH3 (9) was reported to show a slight sensitivity to UV, and a strain with the double deletion of RAD23 and HOF1 or PPH3 showed no typically increased sensitivity to UV, suggesting that PPH3 or HOF1 plays a less important role in the UV response than RAD23. Furthermore, deletion of RAD4 and RAD23 caused sensitivity to UV; however, the RAD4 RAD23 double deletion mutant showed UV sensitivity similar to that of the RAD4 single-deletion strain, consistent with RAD4 and RAD23 functioning in the same pathway in response to UV ( Fig.…”

Section: Deletion Of Rad23 Creates Defects In Cytokinesis and Nuclearmentioning

confidence: 99%

Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in Candida albicans

Dong

et al. 2020

mSphere

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In the pathogenic yeast Candida albicans, the DNA damage response contributes to pathogenicity by regulating cell morphology transitions and maintaining survival in response to DNA damage induced by reactive oxygen species (ROS) in host cells. However, the function of nucleotide excision repair (NER) in C. albicans has not been extensively investigated. To better understand the DNA damage response and its role in virulence, we studied the function of the Rad23 nucleotide excision repair protein in detail. The RAD23 deletion strain and overexpression strain both exhibit UV sensitivity, confirming the critical role of RAD23 in the nucleotide excision repair pathway. Genetic interaction assays revealed that the role of RAD23 in the UV response relies on RAD4 but is independent of RAD53, MMS22, and RAD18. RAD4 and RAD23 have similar roles in regulating cell morphogenesis and biofilm formation; however, only RAD23, but not RAD4, plays a negative role in virulence regulation in a mouse model. We found that the RAD23 deletion strain showed decreased survival in a Candida-macrophage interaction assay. Transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) data further revealed that RAD23, but not RAD4, regulates the transcription of a virulence factor, SUN41, suggesting a unique role of RAD23 in virulence regulation. Taking these observations together, our work reveals that the RAD23related nucleotide excision pathway plays a critical role in the UV response but may not play a direct role in virulence. The virulence-related role of RAD23 may rely on the regulation of several virulence factors, which may give us further understanding about the linkage between DNA damage repair and virulence regulation in C. albicans. IMPORTANCE Candida albicans remains a significant threat to the lives of immunocompromised people. An understanding of the virulence and infection ability of C. albicans cells in the mammalian host may help with clinical treatment and drug discovery. The DNA damage response pathway is closely related to morphology regulation and virulence, as well as the ability to survive in host cells. In this study, we checked the role of the nucleotide excision repair (NER) pathway, the key repair system that functions to remove a large variety of DNA lesions such as those caused by UV light, but whose function has not been well studied in C. albicans. We found that Rad23, but not Rad4, plays a role in virulence that appears independent of the function of the NER pathway. Our research revealed that the NER pathway represented by Rad4/Rad23 may not play a direct role in virulence but that Rad23 may play a unique role in regulating the transcription of virulence genes that may contribute to the virulence of C. albicans. KEYWORDS Candida albicans, Rad23, Rad4, nucleotide excision repair, virulence C andida albicans, whose pathogenicity is related to characteristics such as adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hyphal transition, contact sensing and thigmotrop...