着色性干皮病p48基因增强全基因组修复并抑制紫外线诱导的诱变。
Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.
作者信息
Tang J Y, Hwang B J, Ford J M, Hanawalt P C, Chu G
机构信息
Department of Medicine, Stanford University, California 94305, USA.
出版信息
Mol Cell. 2000 Apr;5(4):737-44. doi: 10.1016/s1097-2765(00)80252-x.
Abstract
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.
摘要
紫外线损伤DNA结合活性（UV-DDB）在一些因p48基因突变导致的着色性干皮病E组个体中缺乏，但其在DNA修复中的作用一直不清楚。我们发现啮齿动物的细胞系和原代组织中UV-DDB也缺乏。p48转染赋予仓鼠细胞UV-DDB，并增强从基因组DNA和一个表达基因的非转录链中去除环丁烷嘧啶二聚体（CPD）。p48的表达抑制了非转录链产生的紫外线诱导突变，但对细胞紫外线敏感性没有影响。这些结果明确了p48在DNA修复中的作用，证明了CPD在诱变中的重要性，并提示如何改进啮齿动物模型以更好地反映人类的癌症易感性。
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Expression of a mammalian DNA photolyase confers light-dependent repair activity and reduces mutations of UV-irradiated shuttle vectors in xeroderma pigmentosum cells.哺乳动物DNA光解酶的表达赋予光依赖性修复活性，并减少着色性干皮病细胞中紫外线照射的穿梭载体的突变。
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