Duplex interrogation by a direct DNA repair protein in search of base damage | |
Yi, Chengqi ; Chen, Baoen ; Qi, Bo ; Zhang, Wen ; Jia, Guifang ; Zhang, Liang ; Li, Charles J. ; Dinner, Aaron R. ; Yang, Cai-Guang ; He, Chuan | |
刊名 | 自然结构与分子生物学
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2012 | |
关键词 | ESCHERICHIA-COLI ALKA MAMMALIAN DNA ENZYME ALKB SUBSTRATE RECOGNITION INTRAHELICAL LESION CRYSTAL-STRUCTURES ALKYLATION DAMAGE UNDAMAGED DNA ACTIVE-SITE GLYCOSYLASE |
DOI | 10.1038/nsmb.2320 |
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.; Biochemistry & Molecular Biology; Biophysics; Cell Biology; SCI(E); PubMed; 15; ARTICLE; 7; 671-+; 19 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/343376] ![]() |
专题 | 生命科学学院 |
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]. 自然结构与分子生物学,2012. |
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.自然结构与分子生物学. |
MLA | Yi, Chengqi,et al."Duplex interrogation by a direct DNA repair protein in search of base damage".自然结构与分子生物学 (2012). |
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