THE COMPLETE SEQUENCE OF THE CODING REGION OF THE ATM GENE REVEALS SIMILARITY TO CELL-CYCLE REGULATORS IN DIFFERENT SPECIES
THE COMPLETE SEQUENCE OF THE CODING REGION OF THE ATM GENE REVEALS SIMILARITY TO CELL-CYCLE REGULATORS IN DIFFERENT SPECIES
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DOI：
10.1093/hmg/4.11.2025
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发表时间：
1995-11-01
影响因子：
3.5
通讯作者：
ROTMAN, G
中科院分区：
文献类型：
--
作者：
SAVITSKY, K;SFEZ, S;ROTMAN, G
共济失调-毛细血管扩张症（A-T）是一种常染色体隐性遗传疾病，涉及小脑变性、免疫缺陷、辐射敏感性和癌症易感性。A-T杂合子有中度癌症倾向。本实验室最近通过定位克隆的方法鉴定了A-T基因，命名为ATM，并发现一个部分cDNA克隆编码一个具有PI-3激酶结构域的多肽。我们在这里报告的分子克隆的cDNA重叠群跨越完整的开放阅读框架的ATM基因。预测的3056个氨基酸的蛋白质显示出显着的序列相似性，在酵母，果蝇和哺乳动物，所有这些共享PI-3激酶结构域中的几个大蛋白。这些蛋白质中的许多参与DNA损伤的检测和细胞周期进程的控制。它们基因中的突变赋予了多种表型，其特征与在人类A-T细胞中观察到的特征相似。ATM基因产物的完整序列为该蛋白质的功能提供了有用的线索，并进一步了解A-T突变的多效性。
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immuno-deficiency, radiation sensitivity, and cancer predisposition. A-T heterozygotes are moderately cancer prone. The A-T gene, designated ATM, was recently identified in our laboratory by positional cloning, and a partial cDNA clone was found to encode a polypeptide with a PI-3 kinase domain. We report here the molecular cloning of a cDNA contig spanning the complete open reading frame of the ATM gene. The predicted protein of 3056 amino acids shows significant sequence similarities to several large proteins in yeast, Drosophila and mammals, ail of which share the PI-3 kinase domain. Many of these proteins are involved in the detection of DNA damage and the control of cell cycle progression. Mutations in their genes confer a variety of phenotypes with features similar to those observed in human A-T cells. The complete sequence of the ATM gene product provides useful clues to the function of this protein, and furthers understanding of the pleiotropic nature of the A-T mutations.