来宝网 2011/7/8点击1826次
上海一基实业有限公司主要从事免疫学、分子生物学和常规生化试剂的研发、销售。并代理销售Sigma、America 、等多个国外知名品牌。
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被烷基化或脱氨基的DNA碱基，在一个保护基因组完整性、但同时又会干预癌症烷基化疗法的过程中被DNA糖基化酶(修复酶)清除。迄今所研究的DNA糖基化酶采用一个被修饰的碱基插入活性点的机制。
现在，最近发现的DNA糖基化酶AlkD的结构已被确定，并且也显示了一个非常不同的机制。按这种机制，被修饰的碱基从一个“螺旋外”位置伸出，这个位置只使N3- 和N7-被烷基化的碱基发生解理。
DNA与AlkD的串联HEAT重复段的相互作用使DNA 骨干发生扭曲，从而使“非Watson–Crick碱基对”能够被检测到。AlkD酶在细菌、古细菌、植物和真核生物中普遍存在，这便提出了一个有趣的问题：为什么消除基因组烷基化损伤会有另一种机制？
英文摘要：
Nature doi:10.1038/nature09428
An unprecedented nucleic acid capture mechanism for excision of DNA damage
Emily H. Rubinson,A. S. Prakasha Gowda,Thomas E. Spratt,Barry Gold& Brandt F. Eichman
DNA glycosylases that remove alkylated and deaminated purine nucleobases are essential DNA repair enzymes that protect the genome, and at the same time confound cancer alkylation therapy, by excising cytotoxic N3-methyladenine bases formed by DNA-targeting anticancer compounds. The basis for glycosylase specificity towards N3- and N7-alkylpurines is believed to result from intrinsic instability of the modified bases and not from direct enzyme functional group chemistry. Here we present crystal structures of the recently discovered Bacillus cereus AlkD glycosylase in complex with DNAs containing alkylated, mismatched and abasic nucleotides. Unlike other glycosylases, AlkD captures the extrahelical lesion in a solvent-exposed orientation, providing an illustration for how hydrolysis of N3- and N7-alkylated bases may be facilitated by increased lifetime out of the DNA helix. The structures and supporting biochemical analysis of base flipping and catalysis reveal how the HEAT repeats of AlkD distort the DNA backbone to detect non-Watson–Crick base pairs without duplex intercalation.
