Damage Detection and Base Flipping in Direct DNA Alkylation Repair
文献类型:期刊论文
作者 | Yang, Cai-Guang1![]() |
刊名 | CHEMBIOCHEM
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出版日期 | 2009-02-13 |
卷号 | 10期号:3页码:417-423 |
关键词 | AlkB DNA damage DNA repair nucleic acids protein-DNA interaction |
ISSN号 | 1439-4227 |
DOI | 10.1002/cbic.200800580 |
文献子类 | Review |
英文摘要 | To remove a few damaged bases efficiently from the context of the entire genome, the DNA base repair proteins rely on remarkably specific detection mechanisms to locate base lesions. This efficient molecular recognition event inside cells has been extensively studied with various structural and biochemical tools. These studies suggest that DNA base damage can be located by repair proteins by using two mechanisms, a repair protein con probe and detect a weakened base pair that results from mutagenic or cytotoxic base damage; alternatively, a protein can passively capture and stabilize an extrahelical base lesion. Our chemical and structural studies on the direct DNA repair proteins hAGT, C-Ada and ABH2 suggest that these proteins search for weakened base pairs in their first step of damage searching. We have also discovered a very unique base-flipping mechanism used by the DNA repair protein AlkB. This protein distorts DNA and favors single stranded DNA (ssDNA) substrates over double-stranded (dsDNA) ones. Potentially, it locates base lesions in dsDNA by imposing a constraint that targets less rigid regions of the duplex DNA. The exact mechanism of how AlkB and related proteins search for damage in ssDNA and dsDNA still awaits further studies. |
WOS关键词 | OXIDATIVE DEMETHYLATION ; ESCHERICHIA-COLI ; CRYSTAL-STRUCTURES ; CROSS-LINKING ; ALKB ; GLYCOSYLASE ; LESIONS ; RECOGNITION ; PROTEINS ; METHYLTRANSFERASES |
资助项目 | National Institutes of Health[GM071440] ; W. M. Keck Foundation Distinguished Young Scholar in Medical Research Program[00000000] ; Arnold and Mabel Beckman Foundation Young Investigator Program[00000000] |
WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
语种 | 英语 |
WOS记录号 | WOS:000263803100002 |
出版者 | WILEY-V C H VERLAG GMBH |
源URL | [http://119.78.100.183/handle/2S10ELR8/279314] ![]() |
专题 | 药理学第三研究室 |
通讯作者 | He, Chuan |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chicago, Dept Chem, Chicago, IL 60637 USA; |
推荐引用方式 GB/T 7714 | Yang, Cai-Guang,Garcia, Kristel,He, Chuan. Damage Detection and Base Flipping in Direct DNA Alkylation Repair[J]. CHEMBIOCHEM,2009,10(3):417-423. |
APA | Yang, Cai-Guang,Garcia, Kristel,&He, Chuan.(2009).Damage Detection and Base Flipping in Direct DNA Alkylation Repair.CHEMBIOCHEM,10(3),417-423. |
MLA | Yang, Cai-Guang,et al."Damage Detection and Base Flipping in Direct DNA Alkylation Repair".CHEMBIOCHEM 10.3(2009):417-423. |
入库方式: OAI收割
来源:上海药物研究所
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