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


ABSTRACT: 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 H2O2, 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.

SUBMITTER: Ma Z 

PROVIDER: S-EPMC7767741 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Ma Zhuang Z   Wang Wentao W   Wang Shiwei S   Zhao Xingqi X   Ma Ying Y   Wu Congye C   Hu Zhigang Z   He Lingfeng L   Pan Feiyan F   Guo Zhigang Z  

Redox biology 20200724


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 s  ...[more]

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