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Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine

文献类型：期刊论文

作者Fu, Tianran1,2; Liu, Liping3,4; Yang, Qing-Lin5; Wang, Yuxin1,2; Xu, Pan3,4; Zhang, Lin1,2; Liu, Shien3,4; Dai, Qing6; Ji, Quanjiang7; Xu, Guo-Liang5
刊名CHEMICAL SCIENCE
出版日期2019-08-21
卷号10期号:31页码:7407-7417
ISSN号2041-6520
DOI10.1039/c9sc02807b
通讯作者Luo, Cheng(cluo@simm.ac.cn) ; Zhang, Liang(liangzhang2014@sjtu.edu.cn)
英文摘要The dynamic DNA methylation-demethylation process plays critical roles in gene expression control and cell development. The oxidation derivatives of 5-methylcytosine (5mC) generated by Tet dioxygenases in the demethylation pathway, namely 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), could impact biological functions by altering DNA properties or recognition by potential reader proteins. Hence, in addition to the fifth base 5mC, 5hmC, 5fC, and 5caC have been considered as the sixth, seventh, and eighth bases of the genome. How these modifications would alter DNA and be specifically recognized remain unclear, however. Here we report that formyl- and carboxyl-modifications on cytosine induce the geometry alteration of the DNA minor groove by solving two high-resolution structures of a dsDNA decamer containing fully symmetric 5fC and 5caC. The alterations are recognized distinctively by thymine DNA glycosylase TDG via its finger residue R275, followed by subsequent preferential base excision and DNA repair. These observations suggest a mechanism by which reader proteins distinguish highly similar cytosine modifications for potential differential demethylation in order to achieve downstream biological functions.
WOS关键词BASE-RESOLUTION ANALYSIS ; CRYSTAL-STRUCTURES ; STRUCTURAL BASIS ; TET PROTEINS ; 5-HYDROXYMETHYLCYTOSINE ; DEMETHYLATION ; EXCISION ; 5-METHYLCYTOSINE ; REFINEMENT ; EXPRESSION
资助项目National Natural Science Foundation of China[21572133] ; National Natural Science Foundation of China[21722802] ; National Natural Science Foundation of China[91853118] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[21820102008] ; National Institutes of Health[HG006827]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000479245400009
出版者ROYAL SOC CHEMISTRY
源URL[http://119.78.100.183/handle/2S10ELR8/288966]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Zhang, Liang
作者单位1.Shanghai Jiao Tong Univ, Sch Med, Dept Pharmacol & Chem Biol, Shanghai, Peoples R China
2.Shanghai Univ Collaborat Innovat Ctr Translat Med, Shanghai, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, CAS Key Lab Receptor Res, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Univ Chinese Acad Sci, State Key Lab Mol Biol, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci,Chinese Acad Sci, Shanghai, Peoples R China
6.Univ Chicago, Dept Biochem & Mol Biol, Dept Chem, Inst Biophys Dynam, 920 E 58Th St, Chicago, IL 60637 USA
7.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Fu, Tianran,Liu, Liping,Yang, Qing-Lin,et al. Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine[J]. CHEMICAL SCIENCE,2019,10(31):7407-7417.
APA Fu, Tianran.,Liu, Liping.,Yang, Qing-Lin.,Wang, Yuxin.,Xu, Pan.,...&Zhang, Liang.(2019).Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine.CHEMICAL SCIENCE,10(31),7407-7417.
MLA Fu, Tianran,et al."Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine".CHEMICAL SCIENCE 10.31(2019):7407-7417.

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来源：上海药物研究所

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