Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis
Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis
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DOI：
10.1016/s1097-2765(00)80252-x
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发表时间：
2000-04-01
期刊：
影响因子：
16
通讯作者：
Chu, G
中科院分区：
文献类型：
--
作者：
Tang, JY;Hwang, BJ;Chu, G
由于p48基因的突变，在某些着色性干皮病E组个体中UV损伤的DNA结合活性（UV-DDB）是缺乏的，但其在DNA修复中的作用一直不清楚。我们发现UV-DDB在啮齿类动物的细胞系和原代组织中也有缺陷。p48的转染赋予UV-DDB仓鼠细胞，并增强从基因组DNA和从非转录链的表达基因的环丁烷嘧啶二聚体（CPD）的去除。p48的表达抑制紫外线诱导的突变所产生的非转录链，但对细胞的紫外线敏感性没有影响。这些结果定义了p48在DNA修复中的作用，证明了CPD在诱变中的重要性，并建议如何改进啮齿动物模型以更好地反映人类的癌症易感性。
UV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma pigmentosum group E individuals due to mutation of the p48 gene, but its role in DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamster cells, and enhanced removal of cyclobutane pyrimidine dimers (CPDs) from genomic DNA and from the nontranscribed strand of an expressed gene. Expression of p48 suppressed UV-induced mutations arising from the nontranscribed strand, but had no effect on cellular UV sensitivity. These results define the role of p48 in DNA repair, demonstrate the importance of CPDs in mutagenesis, and suggest how rodent models can be improved to better reflect cancer susceptibility in humans.