由结构特异性DNA修复内切酶缺陷引起的着色性干皮病F组。

Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease.

作者信息

Sijbers A M, de Laat W L, Ariza R R, Biggerstaff M, Wei Y F, Moggs J G, Carter K C, Shell B K, Evans E, de Jong M C, Rademakers S, de Rooij J, Jaspers N G, Hoeijmakers J H, Wood R D

机构信息

Department of Cell Biology and Genetics, Erasmus University, Rotterdam The Netherlands.

出版信息

Cell. 1996 Sep 6;86(5):811-22. doi: 10.1016/s0092-8674(00)80155-5.

DOI:10.1016/s0092-8674(00)80155-5

PMID:8797827

Abstract

Nucleotide excision repair, which is defective in xeroderma pigmentosum (XP), involves incision of a DNA strand on each side of a lesion. We isolated a human gene homologous to yeast Rad1 and found that it corrects the repair defects of XP group F as well as rodent groups 4 and 11. Causative mutations and strongly reduced levels of encoded protein were identified in XP-F patients. The XPF protein was purified from mammalian cells in a tight complex with ERCC1. This complex is a structure-specific endonuclease responsible for the 5' incision during repair. These results demonstrate that the XPF, ERCC4, and ERCC11 genes are equivalent, complete the isolation of the XP genes that form the core nucleotide excision repair system, and solve the catalytic function of the XPF-containing complex.

摘要

核苷酸切除修复在着色性干皮病（XP）中存在缺陷，它涉及在损伤两侧的DNA链上进行切割。我们分离出了一个与酵母Rad1同源的人类基因，发现它能纠正XP-F组以及啮齿动物4组和11组的修复缺陷。在XP-F患者中鉴定出了致病突变和编码蛋白水平的显著降低。XPF蛋白是从哺乳动物细胞中以与ERCC1紧密结合的复合物形式纯化出来的。这种复合物是一种结构特异性核酸内切酶，负责修复过程中的5'端切割。这些结果表明，XPF、ERCC4和ERCC11基因是等同的，完成了构成核心核苷酸切除修复系统的XP基因的分离，并解决了含XPF复合物的催化功能。