Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1

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成果类型：

期刊论文

作者：

Guo, Hejiang;Han, Yang;Yao, Shibo;Chen, Bijia;Zhao, Hongling;...

通讯作者：

Guan, Hua;Zhou, PK;Lu, J

作者机构：

[Zhou, Ping-Kun; Guo, Hejiang; Han, Yang; Chen, Bijia; Yao, Shibo; Guan, Hua; Zhao, Hongling; Chen, Shi; Liu, Yuhao; Gao, Shanshan; Jia, Jin] Beijing Inst Radiat Med, Dept Radiat Biol, Beijing Key Lab Radiat Biol, Beijing, Peoples R China.

[Zhou, Ping-Kun; Chen, Shi; Jia, Jin] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.

[Lu, Jun] Capital Med Univ, Beijing YouAn Hosp, Dept Med Oncol, Lab Clin Med, Beijing, Peoples R China.

通讯机构：

[Guan, H; Zhou, PK ] B

[Lu, J ] C

Beijing Inst Radiat Med, Dept Radiat Biol, Beijing Key Lab Radiat Biol, Beijing, Peoples R China.

Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.

Capital Med Univ, Beijing YouAn Hosp, Dept Med Oncol, Lab Clin Med, Beijing, Peoples R China.

语种：

英文

关键词：

Crotonylation;HR repair;PARP1;SIRT3;cGAS

期刊：

Journal of Biological Chemistry

ISSN：

0021-9258

年：

2024

卷：

300

期：

页码：

107554

DOI：

10.1016/j.jbc.2024.107554

基金类别：

National Natural Science Foundation of China [82230108, 32171238, 32101165]; Original Exploration Program of the National Natural Science Foundation of China [82150110]

机构署名：

本校为通讯机构

院系归属：

公共卫生学院

摘要：

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, also exhibits nuclear genomic localization and is involved in DNA damage signaling. In this study, we investigated the impact of cGAS crotonylation on the regulation of the DNA damage response, particularly homologous recombination repair, following exposure to ionizing radiation (IR). Lysine 254 of cGAS is constitutively crotonylated by the CREB-binding protein; however, IR-induced DNA damage triggers sirtuin 3 (SIRT3)-mediated decrotonylation. Lysine 254 decrotonylation decreased the DNA-binding affinity of cGAS and inhibited its intera...

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Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1

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