文章：

核苷酸切除修复如何防御癌症

How nucleotide excision repair protects against cancer

原文发布日期：2001-10-01

DOI: 10.1038/35094000

类型: Review Article

开放获取: 否

要点：

1. Living cells respond to DNA damage by a variety of mechanisms, including a series of biochemical pathways called DNA repair. These include three discrete pathways for the excision of damaged bases, called base excision repair, mismatch repair and nucleotide excision repair (NER).
2. NER in human cells is a complex biochemical process during which a large multiprotein complex is assembled at several types of base damage. This multiprotein complex (NER machine) catalyses the excision of damaged bases as oligonucleotide fragments.
3. The RNA polymerase II basal transcription factor, TFIIH, is an integral component of the NER multiprotein complex.
4. NER operates somewhat differently on DNA that is transcriptionally active (transcription-coupled repair) and that which is transcriptionally silent (global genome repair).
5. Defective NER in humans caused by genetically inherited mutations in NER genes results in the skin-cancer-prone disease xeroderma pigmentosum.
6. Hereditary defects in transcription-coupled NER can result in a disease called Cockayne syndrome, which is characterized by severe developmental and neurological disorders.
7. Mutational inactivation of certain NER genes can result in a combined syndrome of xeroderma pigmentosum and Cockayne syndrome, or in yet another disease called trichothiodystrophy, which is characterized by brittle hair and nails.
8. Cockayne syndrome, combined xeroderma pigmentosum/Cockayne syndrome complex and trichothiodystrophy are not usually associated with increased cancer risk.
9. Mouse mutant strains generated by targeted gene replacement have been constructed to model these human NER-defective syndromes.

要点翻译：

1. 活细胞通过多种机制应对DNA损伤，包括一系列称为DNA修复的生化途径。这些途径包含三种不同的损伤碱基切除路径：碱基切除修复、错配修复和核苷酸切除修复（NER）。
2. 在人类细胞中，NER是一个复杂的生化过程，多种碱基损伤会招募大型多蛋白复合体进行组装。这种多蛋白复合体（NER修复机器）能催化受损碱基以寡核苷酸片段形式被切除。
3. RNA聚合酶II基础转录因子TFIIH是NER多蛋白复合体的核心组成部分。
4. NER在转录活跃区域（转录偶联修复）和转录沉默区域（全基因组修复）中的作用机制存在差异。
5. 人类因遗传性NER基因突变导致的NER功能缺陷，会引发易患皮肤癌的着色性干皮病。
6. 转录偶联NER的遗传性缺陷可能导致科凯恩综合征，该病症以严重的发育和神经功能障碍为特征。
7. 特定NER基因的突变失活可能导致着色性干皮病与科凯恩综合征的复合病症，或引发另一种称为毛发硫营养不良的疾病，其特征为毛发和指甲易脆。
8. 科凯恩综合征、着色性干皮病/科凯恩复合征以及毛发硫营养不良通常与癌症风险升高无关。
9. 通过靶向基因替换构建的小鼠突变品系，已被用于模拟这些人类NER缺陷综合征。

英文摘要：

Eukaryotic cells can repair many types of DNA damage. Among the known DNA repair processes in humans, one type — nucleotide excision repair (NER) — specifically protects against mutations caused indirectly by environmental carcinogens. Humans with a hereditary defect in NER suffer from xeroderma pigmentosum and have a marked predisposition to skin cancer caused by sunlight exposure. How does NER protect against skin cancer and possibly other types of environmentally induced cancer in humans?

摘要翻译： 

真核细胞可以修复多种类型的DNA损伤。在人类已知的DNA修复机制中，有一种——核苷酸切除修复（NER）——专门防护由环境致癌物间接引起的突变。NER存在遗传性缺陷的人会患上着色性干皮病，并在日晒后极易发生皮肤癌。NER是如何帮助人类抵御皮肤癌，乃至其他环境因素诱发癌症的？

原文链接：

How nucleotide excision repair protects against cancer