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

doi:10.1039/c9sc02807b

	Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine
	Fu, Tianran 1,2; Liu, Liping 3,4; Yang, Qing-Lin 5; Wang, Yuxin 1,2; Xu, Pan 3,4; Zhang, Lin 1,2; Liu, Shien 3,4; Dai, Qing 6; Ji, Quanjiang 7; Xu, Guo-Liang 5
刊名	CHEMICAL SCIENCE
	2019-08-21
卷号	10 期号:31 页码:7407-7417
ISSN号	2041-6520
DOI	10.1039/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.
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关键词	BASE-RESOLUTION ANALYSIS ; CRYSTAL-STRUCTURES ; STRUCTURAL BASIS ; TET PROTEINS ; 5-HYDROXYMETHYLCYTOSINE ; DEMETHYLATION ; EXCISION ; 5-METHYLCYTOSINE ; REFINEMENT ; EXPRESSION
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000479245400009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288966]
专题	中国科学院上海药物研究所
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.