Cargando…

Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress

The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. 8-oxoguanine DNA glycosylase 1 (OGG1) initiates BER through recognizing and cleaving the oxidatively damaged nucleobase 8-oxo-7,8-dihydroguanine (8-oxoG). How the BER machinery detects and...

Descripción completa

Detalles Bibliográficos
Autores principales: Ma, Zhuang, Wang, Wentao, Wang, Shiwei, Zhao, Xingqi, Ma, Ying, Wu, Congye, Hu, Zhigang, He, Lingfeng, Pan, Feiyan, Guo, Zhigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767741/
https://www.ncbi.nlm.nih.gov/pubmed/32739156
http://dx.doi.org/10.1016/j.redox.2020.101653
_version_ 1783629027252109312
author Ma, Zhuang
Wang, Wentao
Wang, Shiwei
Zhao, Xingqi
Ma, Ying
Wu, Congye
Hu, Zhigang
He, Lingfeng
Pan, Feiyan
Guo, Zhigang
author_facet Ma, Zhuang
Wang, Wentao
Wang, Shiwei
Zhao, Xingqi
Ma, Ying
Wu, Congye
Hu, Zhigang
He, Lingfeng
Pan, Feiyan
Guo, Zhigang
author_sort Ma, Zhuang
collection PubMed
description The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. 8-oxoguanine DNA glycosylase 1 (OGG1) initiates BER through recognizing and cleaving the oxidatively damaged nucleobase 8-oxo-7,8-dihydroguanine (8-oxoG). How the BER machinery detects and accesses lesions within the context of chromatin is largely unknown. Here, we found that the symmetrical dimethylarginine of histone H4 (producing H4R3me2s) serves as a bridge between DNA damage and subsequent repair. Intracellular H4R3me2s was significantly increased after treatment with the DNA oxidant reagent H(2)O(2), and this increase was regulated by OGG1, which could directly interact with the specific arginine methyltransferase, PRMT5. Arginine-methylated H4R3 could associate with flap endonuclease 1 (FEN1) and enhance its nuclease activity and BER efficiency. Furthermore, cells with a decreased level of H4R3me2s were more susceptible to DNA-damaging agents and accumulated more DNA damage lesions in their genome. Taken together, these results demonstrate that H4R3me2s can be recognized as a reader protein that senses DNA damage and a writer protein that promotes DNA repair.
format Online
Article
Text
id pubmed-7767741
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-77677412020-12-29 Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress Ma, Zhuang Wang, Wentao Wang, Shiwei Zhao, Xingqi Ma, Ying Wu, Congye Hu, Zhigang He, Lingfeng Pan, Feiyan Guo, Zhigang Redox Biol Articles from the Special Issue on Redox Signalling and Cardiovascular Disease; Edited by Christopher Kevil and Yabing Chen The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. 8-oxoguanine DNA glycosylase 1 (OGG1) initiates BER through recognizing and cleaving the oxidatively damaged nucleobase 8-oxo-7,8-dihydroguanine (8-oxoG). How the BER machinery detects and accesses lesions within the context of chromatin is largely unknown. Here, we found that the symmetrical dimethylarginine of histone H4 (producing H4R3me2s) serves as a bridge between DNA damage and subsequent repair. Intracellular H4R3me2s was significantly increased after treatment with the DNA oxidant reagent H(2)O(2), and this increase was regulated by OGG1, which could directly interact with the specific arginine methyltransferase, PRMT5. Arginine-methylated H4R3 could associate with flap endonuclease 1 (FEN1) and enhance its nuclease activity and BER efficiency. Furthermore, cells with a decreased level of H4R3me2s were more susceptible to DNA-damaging agents and accumulated more DNA damage lesions in their genome. Taken together, these results demonstrate that H4R3me2s can be recognized as a reader protein that senses DNA damage and a writer protein that promotes DNA repair. Elsevier 2020-07-24 /pmc/articles/PMC7767741/ /pubmed/32739156 http://dx.doi.org/10.1016/j.redox.2020.101653 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles from the Special Issue on Redox Signalling and Cardiovascular Disease; Edited by Christopher Kevil and Yabing Chen
Ma, Zhuang
Wang, Wentao
Wang, Shiwei
Zhao, Xingqi
Ma, Ying
Wu, Congye
Hu, Zhigang
He, Lingfeng
Pan, Feiyan
Guo, Zhigang
Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress
title Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress
title_full Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress
title_fullStr Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress
title_full_unstemmed Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress
title_short Symmetrical dimethylation of H4R3: A bridge linking DNA damage and repair upon oxidative stress
title_sort symmetrical dimethylation of h4r3: a bridge linking dna damage and repair upon oxidative stress
topic Articles from the Special Issue on Redox Signalling and Cardiovascular Disease; Edited by Christopher Kevil and Yabing Chen
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767741/
https://www.ncbi.nlm.nih.gov/pubmed/32739156
http://dx.doi.org/10.1016/j.redox.2020.101653
work_keys_str_mv AT mazhuang symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT wangwentao symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT wangshiwei symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT zhaoxingqi symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT maying symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT wucongye symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT huzhigang symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT helingfeng symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT panfeiyan symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress
AT guozhigang symmetricaldimethylationofh4r3abridgelinkingdnadamageandrepairuponoxidativestress