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Article

Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans

by
Prashant Kumar Maurya
1,†,
Pramita Garai
1,†,
Kaveri Goel
1,
Himanshu Bhatt
1,
Anindita Dutta
1,
Aarti Goyal
1,
Sakshi Dewasthale
1,
Meghna Gupta
2,
Dominic Thangminlen Haokip
3,
Sanju Barik
1 and
Rohini Muthuswami
1,*
1
Chromatin Remodelling Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
2
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA
3
Department of Botany, United College, Chandel, Manipur University, Mizoram 795172, India
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Fungi 2022, 8(6), 559; https://doi.org/10.3390/jof8060559
Submission received: 17 March 2022 / Revised: 27 March 2022 / Accepted: 29 March 2022 / Published: 25 May 2022
(This article belongs to the Section Fungal Genomics, Genetics and Molecular Biology)
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Abstract

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.
Keywords: Rtt109; Fun30; chromatin remodeling; DNA damage response; C. albicans Rtt109; Fun30; chromatin remodeling; DNA damage response; C. albicans

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MDPI and ACS Style

Maurya, P.K.; Garai, P.; Goel, K.; Bhatt, H.; Dutta, A.; Goyal, A.; Dewasthale, S.; Gupta, M.; Haokip, D.T.; Barik, S.; et al. Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans. J. Fungi 2022, 8, 559. https://doi.org/10.3390/jof8060559

AMA Style

Maurya PK, Garai P, Goel K, Bhatt H, Dutta A, Goyal A, Dewasthale S, Gupta M, Haokip DT, Barik S, et al. Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans. Journal of Fungi. 2022; 8(6):559. https://doi.org/10.3390/jof8060559

Chicago/Turabian Style

Maurya, Prashant Kumar, Pramita Garai, Kaveri Goel, Himanshu Bhatt, Anindita Dutta, Aarti Goyal, Sakshi Dewasthale, Meghna Gupta, Dominic Thangminlen Haokip, Sanju Barik, and et al. 2022. "Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans" Journal of Fungi 8, no. 6: 559. https://doi.org/10.3390/jof8060559

APA Style

Maurya, P. K., Garai, P., Goel, K., Bhatt, H., Dutta, A., Goyal, A., Dewasthale, S., Gupta, M., Haokip, D. T., Barik, S., & Muthuswami, R. (2022). Fun30 and Rtt109 Mediate Epigenetic Regulation of the DNA Damage Response Pathway in C. albicans. Journal of Fungi, 8(6), 559. https://doi.org/10.3390/jof8060559

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