Defective replication of psoralen adducts detected at the gene-specific level in xeroderma pigmentosum variant cells.
Defective replication of psoralen adducts detected at the gene-specific level in xeroderma pigmentosum variant cells.
复制标题
在着色性干皮病变异细胞的基因特异性水平上检测到补骨脂素加合物的复制缺陷。
DOI：
10.1128/mcb.13.2.1002-1012.1993
复制
发表时间：
1993
影响因子：
5.3
通讯作者：
Vos,JM
中科院分区：
文献类型：
--
作者：
Misra,RR;Vos,JM
损伤DNA的复制被怀疑在细胞周期、遗传稳定性和存活途径中起重要作用。Vos和Hanawalt先前使用补骨脂素光加成作为原型DNA损伤和复性琼脂糖凝胶电泳技术来测量单个基因中的DNA交联，观察到补骨脂素单加合物在人类基因中的有效旁路复制（J.- M. H. Vos和P.C. Hanawalt，Cell 50：789-799，1987）。为了理解人类细胞中旁路复制的机制，在这种过程中受影响的突变体将是有用的。我们现在报告，细胞从个人患有遗传性隐性综合征着色性干皮病变种（XPV）是过敏的光活化peptide诱导的杀伤。此外，分析的peptien介导的DNA交联的rRNA基因表明，虽然peptien加合物的修复是类似的正常人，XPV细胞明显缺乏的能力，旁路peptien加合物在复制过程中，与正常细胞相比，大约一半的单加合物被绕过在XPV细胞复制过程中。此外，与正常细胞相比，在XPV中未检测到链间交联的复制。这是首次证明在体内基因特异性水平检测到旁路复制缺陷。提出了一个包含链缺陷的XPV重组旁路模型。
Replication of damaged DNA is suspected to play an important role in cell cycle, genetic stability, and survival pathways. Using psoralen photoaddition as prototype DNA damage and the renaturing agarose gel electrophoresis technique to measure DNA cross-linking in individual genes, Vos and Hanawalt previously observed efficient bypass replication of psoralen monoadducts in human genes (J.-M. H. Vos and P. C. Hanawalt, Cell 50:789-799, 1987). To understand the mechanism of bypass replication in human cells, mutants affected in such a process would be useful. We now report that cells from individuals suffering from the hereditary recessive syndrome xeroderma pigmentosum variant (XPV) are hypersensitive to killing induced by photoactivated psoralen. In addition, analysis of psoralen-mediated DNA cross-linking in the rRNA genes indicated that although repair of psoralen adducts was similar to that of normal individuals, XPV cells were markedly deficient in the ability to bypass psoralen adducts during replication; in comparison with normal cells, approximately half as many monoadducts were bypassed during replication in XPV cells. Furthermore, in contrast to normal cells, replication of interstrand cross-links was not detected in XPV. This is the first demonstration of a deficiency in bypass replication detected at the gene-specific level in vivo. A model involving a strand-specific defect in recombinational bypass in XPV is proposed.