Duplex interrogation by a direct DNA repair protein in search of base damage
文献类型：期刊论文
| 作者 | Yi, Chengqi1,4,5,6; Chen, Baoen3; Qi, Bo2,4,5; Zhang, Wen4,5; Jia, Guifang4,5; Zhang, Liang4,5; Li, Charles J.4,5; Dinner, Aaron R.2,4,5; Yang, Cai-Guang3 ; He, Chuan4,5
|
| 刊名 | NATURE STRUCTURAL & MOLECULAR BIOLOGY
 |
| 出版日期 | 2012-07 |
| 卷号 | 19期号:7页码:671-+ |
| ISSN号 | 1545-9993 |
| DOI | 10.1038/nsmb.2320 |
| 文献子类 | Article |
| 英文摘要 | ALKBH2 is a direct DNA repair dioxygenase guarding the mammalian genome against N-1-methyladenine, N-3-methylcytosine and 1,N-6-ethenoadenine damage. A prerequisite for repair is to identify these lesions in the genome. Here we present crystal structures of human ALKBH2 bound to different duplex DNAs. Together with computational and biochemical analyses, our results suggest that DNA interrogation by ALKBH2 has two previously unknown features: (i) ALKBH2 probes base-pair stability and detects base pairs with reduced stability, and (ii) ALKBH2 does not have nor need a damage-checking site, which is critical for preventing spurious base cleavage for several glycosylases. The demethylation mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed to normal bases, and that a flipped, non-substrate base remains intact in the active site. Overall, the combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly. |
| WOS关键词 | ESCHERICHIA-COLI ALKA ; MAMMALIAN DNA ; ENZYME ALKB ; SUBSTRATE RECOGNITION ; INTRAHELICAL LESION ; CRYSTAL-STRUCTURES ; ALKYLATION DAMAGE ; UNDAMAGED DNA ; ACTIVE-SITE ; GLYCOSYLASE |
| 资助项目 | US National Institutes of Health[GM071440] ; Chinese Academy of Sciences[00000000] ; State Key Development Program of Basic Research of China[2009CB918502] ; special grant for Stem Cell and Regenerative Medicine[XDA01040305] ; National Science Foundation[MCB-0547854] ; General Medicine and Cancer Institutes Collaborative Access Team, GM/CA-CAT[00000000] ; Life Sciences Collaborative Access Team, LS-CAT[00000000] ; The Northeastern Collaborative Access Team, NE-CAT) at the Advanced Photon Source at Argonne National Laboratory[00000000] ; Shanghai Synchrotron Radiation Facility[BL17U1] ; US Department of Energy[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000306107100005 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278028]  |
| 专题 | 药理学第三研究室 |
| 通讯作者 | He, Chuan |
| 作者单位 | 1.Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China; 2.Univ Chicago, James Franck Inst, Chicago, IL 60637 USA 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 4.Univ Chicago, Dept Chem, Chicago, IL 60637 USA; 5.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA; 6.Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yi, Chengqi,Chen, Baoen,Qi, Bo,et al. Duplex interrogation by a direct DNA repair protein in search of base damage[J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY,2012,19(7):671-+. |
| APA | Yi, Chengqi.,Chen, Baoen.,Qi, Bo.,Zhang, Wen.,Jia, Guifang.,...&He, Chuan.(2012).Duplex interrogation by a direct DNA repair protein in search of base damage.NATURE STRUCTURAL & MOLECULAR BIOLOGY,19(7),671-+. |
| MLA | Yi, Chengqi,et al."Duplex interrogation by a direct DNA repair protein in search of base damage".NATURE STRUCTURAL & MOLECULAR BIOLOGY 19.7(2012):671-+. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。