title: Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage.
abstract: DNA damage response (DDR) signaling network is initiated to protect cells from various exogenous and endogenous damage resources. Timely and accurate regulation of DDR proteins is required for distinct DNA damage repair pathways. Post-translational modifications of histone and non-histone proteins play a vital role in the DDR factor foci formation and signaling pathway. Phosphorylation, ubiquitylation, SUMOylation, neddylation, poly(ADP-ribosyl)ation, acetylation, and methylation are all involved in the spatial-temporal regulation of DDR, among which phosphorylation and ubiquitylation are well studied. Studies in the past decade also revealed extensive roles of lysine methylation in response to DNA damage. Lysine methylation is finely regulated by plenty of lysine methyltransferases, lysine demethylases, and can be recognized by proteins with chromodomain, plant homeodomain, Tudor domain, malignant brain tumor domain, or proline-tryptophan-tryptophan-proline domain. In this review, we outline the dynamics and regulation of histone lysine methylation at canonical (H3K4, H3K9, H3K27, H3K36, H3K79, and H4K20) and non-canonical sites after DNA damage, and discuss their context-specific functions in DDR protein recruitment or extraction, chromatin environment establishment, and transcriptional regulation. We also present the emerging advances of lysine methylation in non-histone proteins during DDR.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China Peking University-Tsinghua University Center for Life Sciences, Beijing 100191, China.
authors.forename: Yongcan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China Peking University-Tsinghua University Center for Life Sciences, Beijing 100191, China School of Medicine, Shenzhen University, Shenzhen 518060, China zhuweiguo@bjmu.edu.cn.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Zhu
mesh_terms: D004249:DNA Damage; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D054875:Ubiquitination
chemical_list: D006657:Histones; D008239:Lysine
keywords: DNA damage response; histone methylation; lysine methylation