Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage  

作　　者：Yongcan Chen Wei-Guo Zhu 

机构地区：[1]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 [2]Peking University-Tsinghua University Center for Life Sciences, Beijing 100191, China [3]School of Medicine, Shenzhen University, Shenzhen 518060, China

出　　处：《Acta Biochimica et Biophysica Sinica》2016年第7期603-616,共14页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Basic Research Program of China （Nos. 2011CB910100, 2011CB504200, and 2013CB911000）, the National Natural Science Foundation of China （Nos. 81222028, 81321003, 81472581, 81530074, 31570812, and 91319302）, and the Ministry of Science and Technology of China （No. B70001）.

摘　　要：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 phos- phorylation 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.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 phos- phorylation 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.

关 键 词：DNA damage response lysine methylation histone methylation 

分 类 号：Q255[生物学—细胞生物学] Q959.117