Increased UV resistance in xeroderma pigmentosum group A cells after transformation with a human genomic DNA clone.
Increased UV resistance in xeroderma pigmentosum group A cells after transformation with a human genomic DNA clone.
复制标题
用人类基因组 DNA 克隆转化后，着色性干皮病 A 组细胞的抗紫外线能力增强。
DOI：
10.1073/pnas.87.17.6818
复制
发表时间：
1990
影响因子：
11.1
通讯作者：
Lloyd,RS
中科院分区：
文献类型：
--
作者：
Rinaldy,A;Bellew,T;Egli,E;Lloyd,RS
着色性干皮病是一种常染色体隐性遗传病，其主要临床表现是发生阳光诱导的皮肤肿瘤的几率增加2000倍，其分子基础是DNA切除修复系统缺陷。为了克隆XP互补组A缺陷基因(XP-A)，采用竞争杂交法分离了相应的基因克隆，其相应的mRNAs在专性杂合双亲的细胞中比纯合子先证者细胞中更为丰富。在本报告中，一个含有该基因的人基因组DNA克隆被转化到两个独立的纯合子XP-A细胞系中，这些转化子对紫外线照射的杀伤效应表现出部分恢复。与该cdna相对应的mRNA的丰度似乎与观察到的UV细胞存活率有很好的相关性。紫外线照射后的非程序DNA合成结果表明，相对于对照XP-A细胞，转化的细胞具有良好的修复能力。然而，使用同样的基因组DNA，转化XP-F细胞株并不能提高紫外线存活率，也不能促进紫外线照射后非计划DNA的合成。
Xeroderma pigmentosum (XP) is an autosomal recessive disease in which the major clinical manifestation is a 2,000-fold enhanced probability of developing sunlight-induced skin tumors, and the molecular basis for the disease is a defective DNA excision repair system. To clone the gene defective in XP complementation group A (XP-A), cDNA clones were isolated by a competition hybridization strategy in which the corresponding mRNAs were more abundant in cells of the obligately heterozygous parents relative to cells of the homozygous proband affected with the disease. In this report, a human genomic DNA clone that contains this cDNA was transformed into two independent homozygous XP-A cell lines, and these transformants displayed partial restoration of resistance to the killing effects of UV irradiation. The abundance of mRNA corresponding to this cDNA appears to correlate well with the observed UV cell survival. The results of unscheduled DNA synthesis after UV exposure indicate that the transformed cells are repair proficient relative to that of the control XP-A cells. However, using this same genomic DNA, transformation of an XP-F cell line did not confer any enhancement of UV survival or promote unscheduled DNA synthesis after UV exposure.