Friedberg E C
Department of Pathology, Stanford University Medical Center, California 94305.
Cancer Surv. 1985;4(3):529-55.
Little is known about the molecular mechanism of nucleotide excision repair in eukaryotes. Studies on human cells have been stimulated by the availability of excision repair-defective cell lines from patients suffering from the autosomal recessive disease xeroderma pigmentosum. Such studies have contributed appreciably to an understanding of the genetic complexity of excision repair in human cells. However, to date no human excision repair genes or gene products known to complement the repair defect in xeroderma pigmentosum cells have been isolated. The yeast Saccharomyces cerevisiae is an interesting model for exploring the molecular mechanism of nucleotide excision repair in eukaryotic cells. As is true in human cells, multiple yeast genes are involved in this phenomenon and at least five genes are required for the specific incision of ultraviolet-irradiated DNA in vivo. These five genes have been isolated by molecular cloning and the nucleotide sequences of four of them have been determined. Each of these cloned genes will be used for overexpression of protein and it is anticipated that the purification and characterization of these proteins will provide insight into the biochemistry of nucleotide excision repair in eukaryotes.
关于真核生物中核苷酸切除修复的分子机制,人们了解甚少。患有常染色体隐性疾病着色性干皮病患者的切除修复缺陷细胞系的出现,推动了对人类细胞的研究。这类研究对理解人类细胞中切除修复的遗传复杂性有显著贡献。然而,迄今为止,尚未分离出已知可弥补着色性干皮病细胞修复缺陷的人类切除修复基因或基因产物。酿酒酵母是探索真核细胞中核苷酸切除修复分子机制的有趣模型。与人类细胞一样,多种酵母基因参与这一现象,体内紫外线照射的DNA的特异性切割至少需要五个基因。这五个基因已通过分子克隆分离出来,其中四个的核苷酸序列已确定。这些克隆基因中的每一个都将用于蛋白质的过表达,预计这些蛋白质的纯化和特性分析将为真核生物中核苷酸切除修复的生物化学提供深入了解。