Disorders of DNA replication and repair
Disorders of DNA replication and repair
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DOI：
10.1097/00008480-199712000-00010
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发表时间：
1997-12-01
影响因子：
3.6
通讯作者：
Verlander, Peter C.
中科院分区：
文献类型：
--
作者：
Auerbach, Arleen D.;Verlander, Peter C.
大多数涉及 DNA 复制和修复综合征发病机制的基因现已被克隆，并且我们对与许多此类综合征相关的多效性表型基础的理解已迅速而显着地扩展。转录因子复合物 TFIIH 组成的蛋白质之间的特异性相互作用的阐明提出了核苷酸切除修复、RNA 聚合酶 II 转录和细胞周期控制之间存在联系的可能性。 XPB、XPD 和 XPG 基因的缺陷可导致三种不同的综合征：着色性干皮病、科凯恩综合征或毛发硫营养不良，具体取决于所涉及的特定突变。最近对布卢姆综合征（BLM）和沃纳综合征（WRN）相关基因的克隆表明，两者都是DNA和RNA解旋酶，彼此之间以及与其他DExH盒解旋酶具有同源性，但这些基因的缺陷导致如此不同的表型的机制尚不清楚。共济失调毛细血管扩张基因 (ATM) 参与多种信号转导途径，调节细胞对正常增殖刺激的反应以及对 DNA 损伤的反应，这些信号转导途径的破坏为共济失调毛细血管扩张的特征（如电离辐射敏感性、免疫缺陷和不育）提供了解释。尽管第一个范可尼贫血基因 (FAC) 于 5 年前被克隆，第二个范可尼贫血基因 (FAA) 于 1996 年被克隆，但范可尼贫血蛋白的生化功能在很大程度上仍然是个谜。最近针对其中几种疾病构建的突变小鼠品系应该有助于解开这些综合征发病机制的难题。
Most of the genes involved in the pathogenesis of the DNA replication and repair syndromes have now been cloned, and our understanding of the basis for the pleiotropic phenotype associated with many of these syndromes has rapidly and dramatically expanded. The elucidation of the specific interactions between proteins that comprise the transcription factor complex TFIIH raises the possibility that nucleotide excision repair, RNA polymerase II transcription, and cell cycle control are connected. Defects in the XPB, XPD, and XPG genes can result in three different syndromes, xeroderma pigmentosum, Cockayne syndrome, or trichothiodystrophy, depending on the specific mutation involved. The recent cloning of the genes involved in Bloom syndrome (BLM) and Werner syndrome (WRN) show that both are DNA and RNA helicases with homology to each other and to other DExH box helicases, yet the mechanism by which defects in these genes cause such different phenotypes is not yet understood. The ataxia-telangiectasia gene (ATM) is involved in a variety of signal transduction pathways that regulate the cellular response to normal proliferative stimuli as well as the response to DNA damage, and the disruption of these signal transduction pathways provides an explanation for ataxia-telangiectasia characteristics such as ionizing radiation sensitivity, immunodeficiency, and infertility. Although the first Fanconi anemia gene (FAC) was cloned over 5 years ago, and a second Fanconi anemia gene (FAA) was cloned in 1996, the biochemical function of Fanconi anemia proteins largely remains a mystery. The recent construction of mutant mouse strains for several of these diseases should help unlock the difficult puzzle of the pathogenesis of these syndromes.