Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>

ABSTRACT The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoforman...

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Autores principales:	Kwang-Woo Jung, Dong-Hoon Yang, Min-Kyu Kim, Ho Seong Seo, Sangyong Lim, Yong-Sun Bahn
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/020b5872ccc74158960fd4e84f0c631b
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spelling	oai:doaj.org-article:020b5872ccc74158960fd4e84f0c631b2021-11-15T15:50:15ZUnraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>10.1128/mBio.01483-162150-7511https://doaj.org/article/020b5872ccc74158960fd4e84f0c631b2016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01483-16https://doaj.org/toc/2150-7511ABSTRACT The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans. IMPORTANCE Although there are no natural environments under intense radiation, some living organisms have been found to show high radiation resistance. Organisms harboring the ability of radiation resistance have unique regulatory networks to overcome this stress. Cryptococcus neoformans is one of the radiation-resistant fungi and is found in highly radioactive environments. However, it remains elusive how radiation-resistant eukaryotic microorganisms work differentially from radiation-sensitive ones. Here, we performed transcriptome analysis of C. neoformans to explore gene expression profiles after gamma radiation exposure and functionally characterized some of identified radiation resistance genes. Notably, we identified a novel regulator of radiation resistance, named Bdr1 (a bZIP TF for DNA damage response 1), which is a transcription factor (TF) that is not closely homologous to any known TF and is transcriptionally controlled by the Rad53 kinase. Therefore, our work could shed light on understanding not only the radiation response but also the radiation resistance mechanism of C. neoformans.Kwang-Woo JungDong-Hoon YangMin-Kyu KimHo Seong SeoSangyong LimYong-Sun BahnAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kwang-Woo Jung Dong-Hoon Yang Min-Kyu Kim Ho Seong Seo Sangyong Lim Yong-Sun Bahn Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
description	ABSTRACT The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans. IMPORTANCE Although there are no natural environments under intense radiation, some living organisms have been found to show high radiation resistance. Organisms harboring the ability of radiation resistance have unique regulatory networks to overcome this stress. Cryptococcus neoformans is one of the radiation-resistant fungi and is found in highly radioactive environments. However, it remains elusive how radiation-resistant eukaryotic microorganisms work differentially from radiation-sensitive ones. Here, we performed transcriptome analysis of C. neoformans to explore gene expression profiles after gamma radiation exposure and functionally characterized some of identified radiation resistance genes. Notably, we identified a novel regulator of radiation resistance, named Bdr1 (a bZIP TF for DNA damage response 1), which is a transcription factor (TF) that is not closely homologous to any known TF and is transcriptionally controlled by the Rad53 kinase. Therefore, our work could shed light on understanding not only the radiation response but also the radiation resistance mechanism of C. neoformans.
format	article
author	Kwang-Woo Jung Dong-Hoon Yang Min-Kyu Kim Ho Seong Seo Sangyong Lim Yong-Sun Bahn
author_facet	Kwang-Woo Jung Dong-Hoon Yang Min-Kyu Kim Ho Seong Seo Sangyong Lim Yong-Sun Bahn
author_sort	Kwang-Woo Jung
title	Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_short	Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_full	Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_fullStr	Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_full_unstemmed	Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_sort	unraveling fungal radiation resistance regulatory networks through the genome-wide transcriptome and genetic analyses of <named-content content-type="genus-species">cryptococcus neoformans</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/020b5872ccc74158960fd4e84f0c631b
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Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of <named-content content-type="genus-species">Cryptococcus neoformans</named-content>

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