Nucleotide excision repair deficient mouse models and neurological disease
Nucleotide excision repair deficient mouse models and neurological disease
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DOI：
10.1016/j.dnarep.2007.12.006
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发表时间：
2008-07-01
期刊：
影响因子：
3.8
通讯作者：
Niedernhofer, Laura J.
中科院分区：
文献类型：
--
作者：
Niedernhofer, Laura J.
核苷酸切除修复(NER)是一种高度保守的去除螺旋扭曲DNA碱基损伤的机制。NER的一个主要底物是由环境遗传毒素造成的DNA损伤，最明显的是紫外线辐射。色素性干皮病、Cockayne综合征和毛发硫代营养不良是由NER遗传缺陷引起的三种人类疾病。这些疾病的症状和严重程度差异很大，从严重的发育迟缓到癌症易感性和加速衰老。这三种综合征都包括神经系统疾病，这表明NER在保护DNA免受自发损伤方面也发挥了重要作用。为了研究DNA损伤引起的病理生理学，通过敲除NER所需的基因或敲入导致疾病的人类突变，建立了大量NER缺乏的小鼠模型。该综述探讨了这些小鼠模型在研究NER缺乏引起的神经系统疾病方面的应用。(C)2007 Elsevier B.V.保留所有权利。
Nucleotide excision repair (NER) is a highly conserved mechanism to remove helix-distorting DNA base damage. A major substrate for NER is DNA damage caused by environmental genotoxins, most notably ultraviolet radiation. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy are three human diseases caused by inherited defects in NER. The symptoms and severity of these diseases vary dramatically, ranging from profound developmental delay to cancer predisposition and accelerated aging. All three syndromes include neurological disease, indicating an important role for NER in protecting against spontaneous DNA damage as well. To study the pathophysiology caused by DNA damage, numerous mouse models of NER-deficiency were generated by knocking-out genes required for NER or knocking-in disease-causing human mutations. This review explores the utility of these mouse models to study neurological disease caused by NER-deficiency. (C) 2007 Elsevier B.V. All rights reserved.