The Cockayne syndrome group B gene product is involved in cellular repair of 8-hydroxyadenine in DNA
The Cockayne syndrome group B gene product is involved in cellular repair of 8-hydroxyadenine in DNA
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DOI：
10.1074/jbc.m204814200
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发表时间：
2002-08-23
影响因子：
4.8
通讯作者：
Bohr, VA
中科院分区：
文献类型：
--
作者：
Tuo, JS;Jaruga, P;Bohr, VA
Cockayne综合征（CS）是一种人类疾病，其特征是对阳光敏感，严重的神经异常和加速衰老。CS有两个互补基团，CS-A和CS-B。CSB基因编码1493个氨基酸的CSB蛋白。我们以前报道，CSB蛋白参与细胞修复的8-羟基鸟嘌呤，丰富的损伤氧化损伤的DNA和推定的解旋酶基序V/VI的CSB可能在这个过程中发挥作用。本研究探讨了CSB蛋白在8-羟基腺嘌呤（8-OH-Ade）细胞修复中的作用，8-OH-Ade是氧化损伤DNA中的另一种丰富的损伤。CS-B-null细胞和在推定的解旋酶结构域的基序VI中具有定点突变的突变体细胞的提取物在体外切割8-羟基腺嘌呤的效率低于野生型细胞。此外，CS-B-null和基序VI突变体细胞在暴露于2或5戈伊剂量的γ辐射后，在其基因组DNA中积累了比野生型细胞更多的8-羟基腺嘌呤。这些结果表明，CSB蛋白有助于细胞修复的8-OH-阿德和基序VI的推定解旋酶结构域的CSB是需要这种活性。
Cockayne syndrome (CS) is a human disease characterized by sensitivity to sunlight, severe neurological abnormalities, and accelerated aging. CS has two complementation groups, CS-A and CS-B. The CSB gene encodes the CSB protein with 1493 amino acids. We previously reported that the CSB protein is involved in cellular repair of 8-hydroxyguanine, an abundant lesion in oxidatively damaged DNA and that the putative helicase motif V/VI of the CSB may play a role in this process. The present study investigated the role of the CSB protein in cellular repair of 8-hydroxyadenine (8-OH-Ade), another abundant lesion in oxidatively damaged DNA. Extracts of CS-B-null cells and mutant cells with site-directed mutation in the motif VI of the putative helicase domain incised 8-hydroxyadenine in vitro less efficiently than wild type cells. Furthermore, CS-B-null and motif VI mutant cells accumulated more 8-hydroxyadenine in their genomic DNA than wild type cells after exposure to gamma-radiation at doses of 2 or 5 Gy. These results suggest that the CSB protein contributes to cellular repair of 8-OH-Ade and that the motif VI of the putative helicase domain of CSB is required for this activity.