Qiu J, Guan M X, Bailis A M, Shen B
Department of Cell and Tumor Biology, The Beckman Research Institute of City of Hope, Duarte, CA 91010-3000, USA.
Nucleic Acids Res. 1998 Jul 1;26(13):3077-83. doi: 10.1093/nar/26.13.3077.
Two closely related genes, EXO1 and DIN 7, in the budding yeast Saccharomyces cerevisiae have been found to be sequence homologs of the exo1 gene from the fission yeast Schizosaccharomyces pombe . The proteins encoded by these genes belong to the Rad2/XPG and Rad27/FEN-1 families, which are structure-specific nucleases functioning in DNA repair. An XPG nuclease deficiency in humans is one cause of xeroderma pigmentosum and those afflicted display a hypersensitivity to UV light. Deletion of the RAD2 gene in S. cerevisiae also causes UV hypersensitivity, due to a defect in nucleotide excision repair (NER), but residual UV resistance remains. In this report, we describe evidence for the residual repair of UV damage to DNA that is dependent upon Exo1 nuclease. Expression of the EXO1 gene is UV inducible. Genetic analysis indicates that the EXO1 gene is involved in a NER-independent pathway for UV repair, as exo1 rad2 double mutants are more sensitive to UV than either the rad2 or exo1 single mutants. Since the roles of EXO1 in mismatch repair and recombination have been established, double mutants were constructed to examine the possible relationship between the role of EXO1 in UV resistance and its roles in other pathways for repair of UV damaged DNA. The exo1 msh2 , exo1 rad51 , rad2 rad51 and rad2 msh2 double mutants were all more sensitive to UV than their respective pairs of single mutants. This suggests that the observed UV sensitivity of the exo1 deletion mutant is unlikely to be due to its functional deficiencies in MMR, recombination or NER. Further, it suggests that the EXO1 , RAD51 and MSH2 genes control independent mechanisms for the maintenance of UV resistance.
在芽殖酵母酿酒酵母中发现了两个密切相关的基因EXO1和DIN 7，它们是裂殖酵母粟酒裂殖酵母中exo1基因的序列同源物。这些基因编码的蛋白质属于Rad2/XPG和Rad27/FEN - 1家族，它们是在DNA修复中起作用的结构特异性核酸酶。人类XPG核酸酶缺乏是着色性干皮病的一个原因，患者对紫外线敏感。酿酒酵母中RAD2基因的缺失也会导致紫外线超敏反应，这是由于核苷酸切除修复（NER）缺陷，但仍保留一定的紫外线抗性。在本报告中，我们描述了依赖于Exo1核酸酶的DNA紫外线损伤残留修复的证据。EXO1基因的表达是紫外线诱导的。遗传分析表明，EXO1基因参与了一条不依赖NER的紫外线修复途径，因为exo1 rad2双突变体比rad2或exo1单突变体对紫外线更敏感。由于EXO1在错配修复和重组中的作用已得到证实，构建了双突变体以研究EXO1在紫外线抗性中的作用与其在其他紫外线损伤DNA修复途径中的作用之间的可能关系。exo1 msh2、exo1 rad51、rad2 rad51和rad2 msh2双突变体对紫外线的敏感性均高于各自的单突变体对。这表明观察到的exo1缺失突变体的紫外线敏感性不太可能是由于其在错配修复、重组或NER中的功能缺陷。此外，这表明EXO1、RAD51和MSH2基因控制着维持紫外线抗性的独立机制。
