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DNA聚合酶β的活性与机制

Activities and mechanism of DNA polymerase beta.

作者信息

Beard William A, Prasad Rajendra, Wilson Samuel H

机构信息

Enzymology Section, Laboratory of Structural Biology, NIEHS-NIH, North Carolina, USA.

出版信息

Methods Enzymol. 2006;408:91-107. doi: 10.1016/S0076-6879(06)08007-4.

DOI:10.1016/S0076-6879(06)08007-4
PMID:16793365
Abstract

DNA polymerase beta plays an essential role in the base excision repair pathway necessary to cleanse the genome of simple base lesions and abasic sites. Abasic sites arise in DNA from spontaneous base loss (depurination) and DNA-damage specific glycosylases that hydrolyze the N-glycosidic bond between the deoxyribose and the damaged base. DNA polymerase beta contributes two enzymatic activities: DNA synthesis and deoxyribose-phosphate removal through nucleotidyl transferase and lyase mechanisms, respectively. The active site for each of these activities resides on a distinct domain of the protein: 31-kDa polymerase domain and amino-terminal 8-kDa lyase domain. The simple organization of each domain and the ability to assay each activity have hastened our understanding of the faithful replication of DNA during repair synthesis and the flux of intermediates through single nucleotide base excision repair and its alternate pathways.

摘要

DNA聚合酶β在碱基切除修复途径中起着至关重要的作用,该途径对于清除基因组中的简单碱基损伤和无碱基位点是必需的。无碱基位点在DNA中由自发碱基丢失(脱嘌呤)和水解脱氧核糖与受损碱基之间N-糖苷键的DNA损伤特异性糖基化酶产生。DNA聚合酶β具有两种酶活性:分别通过核苷酸转移酶和裂解酶机制进行DNA合成和脱氧核糖磷酸去除。这些活性各自的活性位点位于蛋白质的不同结构域上:31 kDa聚合酶结构域和氨基末端8 kDa裂解酶结构域。每个结构域的简单组织以及检测每种活性的能力加快了我们对修复合成过程中DNA忠实复制以及通过单核苷酸碱基切除修复及其替代途径的中间体通量的理解。

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