Takayama K, Salazar E P, Lehmann A, Stefanini M, Thompson L H, Weber C A
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94551, USA.
Cancer Res. 1995 Dec 1;55(23):5656-63.
Xeroderma pigmentosum (XP) is a sun-sensitive, cancer-prone genetic disorder characterized by a defect in nucleotide excision repair. The human nucleotide excision repair and transcription gene ERCC2 is able to restore survival to normal levels after exposure to UV light in XP complementation group D cells. No enhancement of UV survival is seen in groups C, E, F, or G. XP-CS-2 cells are complemented by ERCC2, confirming the reassignment to group D of this combined XP/Cockayne's syndrome patient. Nucleotide sequence analysis of the ERCC2 cDNA from five XP group D cell strains [XP6BE(SV40), XP17PV, XP102LO, A31-27 (a HeLa/XP102LO hybrid), and XP-CS-2] revealed mutations predominantly affecting previously identified functional domains. The mutations include base substitutions resulting in amino acid substitutions, deletions due to splicing alterations, and defects in expression. XP6BE(SV40), XP17PV, XP102LO, and A31-27 all have one allele with an Arg683 to Trp substitution within the putative nuclear location signal. The genetic disorder trichothiodystrophy (which is not cancer-prone) can also result from mutations in the ERCC2 gene, some of which are the same as those found in XP-D. The various clinical presentations can be correlated with the particular mutations found in the ERCC2 locus.
着色性干皮病（XP）是一种对阳光敏感、易患癌症的遗传性疾病，其特征在于核苷酸切除修复缺陷。人类核苷酸切除修复和转录基因ERCC2能够使XP互补组D细胞在暴露于紫外线后恢复到正常水平的存活率。在C、E、F或G组中未观察到紫外线存活率的提高。XP-CS-2细胞可被ERCC2互补，证实了这名合并有XP/科凯恩综合征患者被重新归类为D组。对来自五个XP D组细胞系[XP6BE(SV40)、XP17PV、XP102LO、A31-27（一种HeLa/XP102LO杂交细胞）和XP-CS-2]的ERCC2 cDNA进行核苷酸序列分析，发现突变主要影响先前确定的功能域。这些突变包括导致氨基酸取代的碱基替换、由于剪接改变引起的缺失以及表达缺陷。XP6BE(SV40)、XP17PV、XP102LO和A31-27在假定的核定位信号内均有一个等位基因发生了从Arg683到Trp的替换。遗传性疾病毛发硫营养不良症（不易患癌症）也可能由ERCC2基因突变引起，其中一些与在XP-D中发现的突变相同。各种临床表现可与在ERCC2基因座中发现的特定突变相关联。
