Yuasa M, Masutani C, Eki T, Hanaoka F
Institute for Molecular and Cellular Biology, Osaka University and CREST, Japan Science and Technology Corporation, Suita.
Oncogene. 2000 Sep 28;19(41):4721-8. doi: 10.1038/sj.onc.1203842.
The xeroderma pigmentosum variant (XP-V) is one of the most common forms of this cancer-prone syndrome. XP groups A through G are characterized by defective nucleotide excision repair, whereas the XP-V phenotype is proficient in this pathway. The XPV gene encodes DNA polymerase eta, which catalyzes an accurate translesion synthesis, indicating that the XPV gene contributes tumor suppression in normal individuals. Here we describe the genomic structure and chromosomal localization of the XPV gene, which includes 11 exons covering the entire coding sequence, lacks a TATA sequence in the upstream region of the transcription-initiation, and is located at the chromosome band 6p21.1-6p12. Analyses of patient-derived XP-V cell lines strongly suggested that three of four cell lines carried homozygous mutations in the XPV gene. The fourth cell line, XP1RO, carried heterozygous point mutations in the XPV gene, one of which was located at the splice acceptor site of exon 2, resulting in the omission of exon 2 from the mature mRNA. These findings provide a basis for diagnosis and therapy of XP-V patients.
着色性干皮病变异型（XP-V）是这种易患癌症综合征最常见的形式之一。A至G组的着色性干皮病的特征是核苷酸切除修复缺陷，而XP-V表型在该途径中功能正常。XPV基因编码DNA聚合酶η，它催化精确的跨损伤合成，这表明XPV基因在正常个体中有助于肿瘤抑制。在这里，我们描述了XPV基因的基因组结构和染色体定位，该基因包括11个外显子，覆盖整个编码序列，转录起始上游区域缺乏TATA序列，位于染色体6p21.1-6p12带。对患者来源的XP-V细胞系的分析强烈表明，四个细胞系中的三个在XPV基因中携带纯合突变。第四个细胞系XP1RO在XPV基因中携带杂合点突变，其中一个位于外显子2的剪接受体位点，导致成熟mRNA中外显子2缺失。这些发现为XP-V患者的诊断和治疗提供了依据。
