Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair
文献类型：期刊论文
| 作者 | Li, YQ; Zhou, PZ; Zheng, XD; Walsh, CP; Xu, GL |
| 刊名 | NUCLEIC ACIDS RESEARCH
 |
| 出版日期 | 2007 |
| 卷号 | 35期号:2页码:390-400 |
| 通讯作者 | Xu, GL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,glxu@sibs.ac.cn |
| 英文摘要 | While methylcytosines serve as the fifth base encoding epigenetic information, they are also a dangerous endogenous mutagen due to their intrinsic instability. Methylcytosine undergoes spontaneous deamination, at a rate much higher than cytosine, to generate thymine. In mammals, two repair enzymes, thymine DNA glycosylase (TDG) and methyl-CpG binding domain 4 (MBD4), have evolved to counteract the mutagenic effect of methylcytosines. Both recognize G/T mismatches arising from methylcytosine deamination and initiate base-excision repair that corrects them to G/C pairs. However, the mechanism by which the methylation status of the repaired cytosines is restored has remained unknown. We show here that the DNA methyltransferase Dnmt3a interacts with TDG. Both the PWWP domain and the catalytic domain of Dnmt3a are able to mediate the interaction with TDG at its N-terminus. The interaction affects the enzymatic activity of both proteins: Dnmt3a positively regulates the glycosylase activity of TDG, while TDG inhibits the methylation activity of Dnmt3a in vitro. These data suggest a mechanistic link between DNA repair and remethylation at sites affected by methylcytosine deamination. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | METHYLTRANSFERASE DNMT3B ; TRANSITION MUTATIONS ; CYTOSINE METHYLATION ; CPG DINUCLEOTIDE ; PWWP DOMAIN ; SITES ; DEAMINATION ; PROTEIN ; GENE ; TRANSCRIPTION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000243993600010 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1535]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Li, YQ,Zhou, PZ,Zheng, XD,et al. Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair[J]. NUCLEIC ACIDS RESEARCH,2007,35(2):390-400. |
| APA | Li, YQ,Zhou, PZ,Zheng, XD,Walsh, CP,&Xu, GL.(2007).Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair.NUCLEIC ACIDS RESEARCH,35(2),390-400. |
| MLA | Li, YQ,et al."Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair".NUCLEIC ACIDS RESEARCH 35.2(2007):390-400. |
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