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Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae

Cellular metabolism is directly or indirectly associated with various cellular processes by producing a variety of metabolites. Metabolic alterations may cause adverse effects on cell viability. However, some alterations potentiate the rescue of the malfunction of the cell system. Here, we found tha...

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Autores principales: Hanasaki, Miki, Yaku, Keisuke, Yamauchi, Motohiro, Nakagawa, Takashi, Masumoto, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713361/
https://www.ncbi.nlm.nih.gov/pubmed/33273685
http://dx.doi.org/10.1038/s41598-020-78302-5
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author Hanasaki, Miki
Yaku, Keisuke
Yamauchi, Motohiro
Nakagawa, Takashi
Masumoto, Hiroshi
author_facet Hanasaki, Miki
Yaku, Keisuke
Yamauchi, Motohiro
Nakagawa, Takashi
Masumoto, Hiroshi
author_sort Hanasaki, Miki
collection PubMed
description Cellular metabolism is directly or indirectly associated with various cellular processes by producing a variety of metabolites. Metabolic alterations may cause adverse effects on cell viability. However, some alterations potentiate the rescue of the malfunction of the cell system. Here, we found that the alteration of glucose metabolism suppressed genome instability caused by the impairment of chromatin structure. Deletion of the TDH2 gene, which encodes glyceraldehyde 3-phospho dehydrogenase and is essential for glycolysis/gluconeogenesis, partially suppressed DNA damage sensitivity due to chromatin structure, which was persistently acetylated histone H3 on lysine 56 in cells with deletions of both HST3 and HST4, encoding NAD(+)-dependent deacetylases. tdh2 deletion also restored the short replicative lifespan of cells with deletion of sir2, another NAD(+)-dependent deacetylase, by suppressing intrachromosomal recombination in rDNA repeats increased by the unacetylated histone H4 on lysine 16. tdh2 deletion also suppressed recombination between direct repeats in hst3∆ hst4∆ cells by suppressing the replication fork instability that leads to both DNA deletions among repeats. We focused on quinolinic acid (QUIN), a metabolic intermediate in the de novo nicotinamide adenine dinucleotide (NAD(+)) synthesis pathway, which accumulated in the tdh2 deletion cells and was a candidate metabolite to suppress DNA replication fork instability. Deletion of QPT1, quinolinate phosphoribosyl transferase, elevated intracellular QUIN levels and partially suppressed the DNA damage sensitivity of hst3∆ hst4∆ cells as well as tdh2∆ cells. qpt1 deletion restored the short replicative lifespan of sir2∆ cells by suppressing intrachromosomal recombination among rDNA repeats. In addition, qpt1 deletion could suppress replication fork slippage between direct repeats. These findings suggest a connection between glucose metabolism and genomic stability.
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spelling pubmed-77133612020-12-03 Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae Hanasaki, Miki Yaku, Keisuke Yamauchi, Motohiro Nakagawa, Takashi Masumoto, Hiroshi Sci Rep Article Cellular metabolism is directly or indirectly associated with various cellular processes by producing a variety of metabolites. Metabolic alterations may cause adverse effects on cell viability. However, some alterations potentiate the rescue of the malfunction of the cell system. Here, we found that the alteration of glucose metabolism suppressed genome instability caused by the impairment of chromatin structure. Deletion of the TDH2 gene, which encodes glyceraldehyde 3-phospho dehydrogenase and is essential for glycolysis/gluconeogenesis, partially suppressed DNA damage sensitivity due to chromatin structure, which was persistently acetylated histone H3 on lysine 56 in cells with deletions of both HST3 and HST4, encoding NAD(+)-dependent deacetylases. tdh2 deletion also restored the short replicative lifespan of cells with deletion of sir2, another NAD(+)-dependent deacetylase, by suppressing intrachromosomal recombination in rDNA repeats increased by the unacetylated histone H4 on lysine 16. tdh2 deletion also suppressed recombination between direct repeats in hst3∆ hst4∆ cells by suppressing the replication fork instability that leads to both DNA deletions among repeats. We focused on quinolinic acid (QUIN), a metabolic intermediate in the de novo nicotinamide adenine dinucleotide (NAD(+)) synthesis pathway, which accumulated in the tdh2 deletion cells and was a candidate metabolite to suppress DNA replication fork instability. Deletion of QPT1, quinolinate phosphoribosyl transferase, elevated intracellular QUIN levels and partially suppressed the DNA damage sensitivity of hst3∆ hst4∆ cells as well as tdh2∆ cells. qpt1 deletion restored the short replicative lifespan of sir2∆ cells by suppressing intrachromosomal recombination among rDNA repeats. In addition, qpt1 deletion could suppress replication fork slippage between direct repeats. These findings suggest a connection between glucose metabolism and genomic stability. Nature Publishing Group UK 2020-12-03 /pmc/articles/PMC7713361/ /pubmed/33273685 http://dx.doi.org/10.1038/s41598-020-78302-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hanasaki, Miki
Yaku, Keisuke
Yamauchi, Motohiro
Nakagawa, Takashi
Masumoto, Hiroshi
Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
title Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
title_full Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
title_fullStr Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
title_full_unstemmed Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
title_short Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
title_sort deletion of the gapdh gene contributes to genome stability in saccharomyces cerevisiae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713361/
https://www.ncbi.nlm.nih.gov/pubmed/33273685
http://dx.doi.org/10.1038/s41598-020-78302-5
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