RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair

	RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair
	Xiao, YX; Li, JY; Liao, XY; He, YM; He, T; Yang, CP; Jiang, L; Jeon, SM; Lee, JH; Chen, YB; Liu, R; Chen, QM
	2022
发表期刊	BONE RESEARCH
ISSN	2095-4700
卷号	10 期号:1
摘要	Exposure to radiation causes DNA damage; hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1 (RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination (HR) repair but not nonhomologous end-joining (NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase (cGAS) to release cGAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29 (SGF29), which subsequently enables cGAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1 (PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains cGAS K491me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of cGAS that is essential for the regulation of ionizing radiation-elicited HR repair.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13286
专题	科研部门_肿瘤信号转导（陈勇彬）
推荐引用方式 GB/T 7714	Xiao, YX,Li, JY,Liao, XY,et al. RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair[J]. BONE RESEARCH,2022,10(1).
APA	Xiao, YX.,Li, JY.,Liao, XY.,He, YM.,He, T.,...&Chen, QM.(2022).RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair.BONE RESEARCH,10(1).
MLA	Xiao, YX,et al."RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair".BONE RESEARCH 10.1(2022).

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