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Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans
Fun30, an ATP-dependent chromatin remodeler from S. cerevisiae, is known to mediate both regulation of gene expression as well as DNA damage response/repair. The Fun30 from C. albicans has not yet been elucidated. We show that C. albicans Fun30 is functionally homologous to both S. cerevisiae Fun30...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225650/ https://www.ncbi.nlm.nih.gov/pubmed/35736042 http://dx.doi.org/10.3390/jof8060559 |
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author | Maurya, Prashant Kumar Garai, Pramita Goel, Kaveri Bhatt, Himanshu Dutta, Anindita Goyal, Aarti Dewasthale, Sakshi Gupta, Meghna Haokip, Dominic Thangminlen Barik, Sanju Muthuswami, Rohini |
author_facet | Maurya, Prashant Kumar Garai, Pramita Goel, Kaveri Bhatt, Himanshu Dutta, Anindita Goyal, Aarti Dewasthale, Sakshi Gupta, Meghna Haokip, Dominic Thangminlen Barik, Sanju Muthuswami, Rohini |
author_sort | Maurya, Prashant Kumar |
collection | PubMed |
description | Fun30, an ATP-dependent chromatin remodeler from S. cerevisiae, is known to mediate both regulation of gene expression as well as DNA damage response/repair. The Fun30 from C. albicans has not yet been elucidated. We show that C. albicans Fun30 is functionally homologous to both S. cerevisiae Fun30 and human SMARCAD1. Further, C. albicans Fun30 can mediate double-strand break end resection as well as regulate gene expression. This protein regulates transcription of RTT109, TEL1, MEC1, and SNF2-genes that encode for proteins involved in DNA damage response and repair pathways. The regulation mediated by C. albicans Fun30 is dependent on its ATPase activity. The expression of FUN30, in turn, is regulated by histone H3K56 acetylation catalyzed by Rtt109 and encoded by RTT109. The RTT109Hz/FUN30Hz mutant strain shows sensitivity to oxidative stress and resistance to MMS as compared to the wild-type strain. Quantitative PCR showed that the sensitivity to oxidative stress results from downregulation of MEC1, RAD9, MRC1, and RAD5 expression; ChIP experiments showed that Fun30 but not H3K56ac regulates the expression of these genes in response to oxidative stress. In contrast, upon treatment with MMS, the expression of RAD9 is upregulated, which is modulated by both Fun30 and H3K56 acetylation. Thus, Fun30 and H3K56 acetylation mediate the response to genotoxic agents in C. albicans by regulating the expression of DNA damage response and repair pathway genes. |
format | Online Article Text |
id | pubmed-9225650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92256502022-06-24 Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans Maurya, Prashant Kumar Garai, Pramita Goel, Kaveri Bhatt, Himanshu Dutta, Anindita Goyal, Aarti Dewasthale, Sakshi Gupta, Meghna Haokip, Dominic Thangminlen Barik, Sanju Muthuswami, Rohini J Fungi (Basel) Article Fun30, an ATP-dependent chromatin remodeler from S. cerevisiae, is known to mediate both regulation of gene expression as well as DNA damage response/repair. The Fun30 from C. albicans has not yet been elucidated. We show that C. albicans Fun30 is functionally homologous to both S. cerevisiae Fun30 and human SMARCAD1. Further, C. albicans Fun30 can mediate double-strand break end resection as well as regulate gene expression. This protein regulates transcription of RTT109, TEL1, MEC1, and SNF2-genes that encode for proteins involved in DNA damage response and repair pathways. The regulation mediated by C. albicans Fun30 is dependent on its ATPase activity. The expression of FUN30, in turn, is regulated by histone H3K56 acetylation catalyzed by Rtt109 and encoded by RTT109. The RTT109Hz/FUN30Hz mutant strain shows sensitivity to oxidative stress and resistance to MMS as compared to the wild-type strain. Quantitative PCR showed that the sensitivity to oxidative stress results from downregulation of MEC1, RAD9, MRC1, and RAD5 expression; ChIP experiments showed that Fun30 but not H3K56ac regulates the expression of these genes in response to oxidative stress. In contrast, upon treatment with MMS, the expression of RAD9 is upregulated, which is modulated by both Fun30 and H3K56 acetylation. Thus, Fun30 and H3K56 acetylation mediate the response to genotoxic agents in C. albicans by regulating the expression of DNA damage response and repair pathway genes. MDPI 2022-05-25 /pmc/articles/PMC9225650/ /pubmed/35736042 http://dx.doi.org/10.3390/jof8060559 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maurya, Prashant Kumar Garai, Pramita Goel, Kaveri Bhatt, Himanshu Dutta, Anindita Goyal, Aarti Dewasthale, Sakshi Gupta, Meghna Haokip, Dominic Thangminlen Barik, Sanju Muthuswami, Rohini Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans |
title | Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans |
title_full | Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans |
title_fullStr | Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans |
title_full_unstemmed | Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans |
title_short | Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans |
title_sort | fun30 and rtt109 mediate epigenetic regulation of the dna damage response pathway in c. albicans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225650/ https://www.ncbi.nlm.nih.gov/pubmed/35736042 http://dx.doi.org/10.3390/jof8060559 |
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