Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation

Summary: The Krebs cycle enzyme fumarase, which has been identified as a tumor suppressor, is involved in the deoxyribonucleic acid (DNA) damage response (DDR) in human, yeast, and bacterial cells. We have found that the overexpression of the cysteine desulfurase Nfs1p restores DNA repair in fumaras...

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Autores principales:	Joyce Yip, Suqing Wang, Jasper Tan, Teck Kwang Lim, Qingsong Lin, Zhang Yu, Ofri Karmon, Ophry Pines, Norbert Lehming
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Biochemistry Molecular biology Science Q
Acceso en línea:	https://doaj.org/article/0639e65a65ca4316b1912804c974f2a4
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spelling	oai:doaj.org-article:0639e65a65ca4316b1912804c974f2a42021-11-20T05:10:33ZFumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation2589-004210.1016/j.isci.2021.103354https://doaj.org/article/0639e65a65ca4316b1912804c974f2a42021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013237https://doaj.org/toc/2589-0042Summary: The Krebs cycle enzyme fumarase, which has been identified as a tumor suppressor, is involved in the deoxyribonucleic acid (DNA) damage response (DDR) in human, yeast, and bacterial cells. We have found that the overexpression of the cysteine desulfurase Nfs1p restores DNA repair in fumarase-deficient yeast cells. Nfs1p accumulates inactivating post-translational modifications in yeast cells lacking fumarase under conditions of DNA damage. Our model is that in addition to metabolic signaling of the DDR in the nucleus, fumarase affects the DDR by protecting the desulfurase Nfs1p in mitochondria from modification and inactivation. Fumarase performs this protection by directly binding to Nfs1p in mitochondria and enabling, the maintenance, via metabolism, of a non-oxidizing environment in mitochondria. Nfs1p is required for the formation of Fe–S clusters, which are essential cofactors for DNA repair enzymes. Thus, we propose that the overexpression of Nfs1p overcomes the lack of fumarase by enhancing the activity of DNA repair enzymes.Joyce YipSuqing WangJasper TanTeck Kwang LimQingsong LinZhang YuOfri KarmonOphry PinesNorbert LehmingElsevierarticleBiological sciencesBiochemistryMolecular biologyScienceQENiScience, Vol 24, Iss 11, Pp 103354- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Biochemistry Molecular biology Science Q
spellingShingle	Biological sciences Biochemistry Molecular biology Science Q Joyce Yip Suqing Wang Jasper Tan Teck Kwang Lim Qingsong Lin Zhang Yu Ofri Karmon Ophry Pines Norbert Lehming Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation
description	Summary: The Krebs cycle enzyme fumarase, which has been identified as a tumor suppressor, is involved in the deoxyribonucleic acid (DNA) damage response (DDR) in human, yeast, and bacterial cells. We have found that the overexpression of the cysteine desulfurase Nfs1p restores DNA repair in fumarase-deficient yeast cells. Nfs1p accumulates inactivating post-translational modifications in yeast cells lacking fumarase under conditions of DNA damage. Our model is that in addition to metabolic signaling of the DDR in the nucleus, fumarase affects the DDR by protecting the desulfurase Nfs1p in mitochondria from modification and inactivation. Fumarase performs this protection by directly binding to Nfs1p in mitochondria and enabling, the maintenance, via metabolism, of a non-oxidizing environment in mitochondria. Nfs1p is required for the formation of Fe–S clusters, which are essential cofactors for DNA repair enzymes. Thus, we propose that the overexpression of Nfs1p overcomes the lack of fumarase by enhancing the activity of DNA repair enzymes.
format	article
author	Joyce Yip Suqing Wang Jasper Tan Teck Kwang Lim Qingsong Lin Zhang Yu Ofri Karmon Ophry Pines Norbert Lehming
author_facet	Joyce Yip Suqing Wang Jasper Tan Teck Kwang Lim Qingsong Lin Zhang Yu Ofri Karmon Ophry Pines Norbert Lehming
author_sort	Joyce Yip
title	Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation
title_short	Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation
title_full	Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation
title_fullStr	Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation
title_full_unstemmed	Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation
title_sort	fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase nfs1p from modification and inactivation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/0639e65a65ca4316b1912804c974f2a4
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Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation

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