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Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation
Histone methylation regulates DNA repair. However, the mechanisms that underlie the regulation of histone methylation during this repair remain to be further defined. Here, we show that ionizing radiation (IR) induces DNA-PK-dependent phosphorylation of nuclear fumarase at T236, which leads to an in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800990/ https://www.ncbi.nlm.nih.gov/pubmed/26237645 http://dx.doi.org/10.1038/ncb3209 |
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author | Jiang, Yuhui Qian, Xu Shen, Jianfeng Wang, Yugang Li, Xinjian Liu, Rui Xia, Yan Chen, Qianming Peng, Guang Lin, Shiaw-Yih Lu, Zhimin |
author_facet | Jiang, Yuhui Qian, Xu Shen, Jianfeng Wang, Yugang Li, Xinjian Liu, Rui Xia, Yan Chen, Qianming Peng, Guang Lin, Shiaw-Yih Lu, Zhimin |
author_sort | Jiang, Yuhui |
collection | PubMed |
description | Histone methylation regulates DNA repair. However, the mechanisms that underlie the regulation of histone methylation during this repair remain to be further defined. Here, we show that ionizing radiation (IR) induces DNA-PK-dependent phosphorylation of nuclear fumarase at T236, which leads to an interaction between fumarase and the histone variant H2A.Z at DNA double-strand break (DSB) regions. Locally generated fumarate inhibits KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 K36; in turn, this increases the accumulation of the Ku70-containing DNA-PK at DSB regions for non-homologous end joining (NHEJ) DNA repair and cell survival. These findings reveal a feedback mechanism that underlies DNA-PK regulation by chromatin-associated fumarase and an instrumental function of fumarase in regulating histone H3 methylation and DNA repair. |
format | Online Article Text |
id | pubmed-4800990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48009902016-03-21 Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation Jiang, Yuhui Qian, Xu Shen, Jianfeng Wang, Yugang Li, Xinjian Liu, Rui Xia, Yan Chen, Qianming Peng, Guang Lin, Shiaw-Yih Lu, Zhimin Nat Cell Biol Article Histone methylation regulates DNA repair. However, the mechanisms that underlie the regulation of histone methylation during this repair remain to be further defined. Here, we show that ionizing radiation (IR) induces DNA-PK-dependent phosphorylation of nuclear fumarase at T236, which leads to an interaction between fumarase and the histone variant H2A.Z at DNA double-strand break (DSB) regions. Locally generated fumarate inhibits KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 K36; in turn, this increases the accumulation of the Ku70-containing DNA-PK at DSB regions for non-homologous end joining (NHEJ) DNA repair and cell survival. These findings reveal a feedback mechanism that underlies DNA-PK regulation by chromatin-associated fumarase and an instrumental function of fumarase in regulating histone H3 methylation and DNA repair. 2015-08-03 2015-09 /pmc/articles/PMC4800990/ /pubmed/26237645 http://dx.doi.org/10.1038/ncb3209 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Jiang, Yuhui Qian, Xu Shen, Jianfeng Wang, Yugang Li, Xinjian Liu, Rui Xia, Yan Chen, Qianming Peng, Guang Lin, Shiaw-Yih Lu, Zhimin Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation |
title | Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation |
title_full | Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation |
title_fullStr | Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation |
title_full_unstemmed | Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation |
title_short | Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation |
title_sort | local generation of fumarate promotes dna repair through inhibition of histone h3 demethylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800990/ https://www.ncbi.nlm.nih.gov/pubmed/26237645 http://dx.doi.org/10.1038/ncb3209 |
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