A SINGLE ATAXIA-TELANGIECTASIA GENE WITH A PRODUCT SIMILAR TO PI-3 KINASE
A SINGLE ATAXIA-TELANGIECTASIA GENE WITH A PRODUCT SIMILAR TO PI-3 KINASE
复制标题
DOI：
10.1126/science.7792600
复制
发表时间：
1995-06-23
期刊：
影响因子：
56.9
通讯作者：
SHILOH, Y
中科院分区：
文献类型：
--
作者：
SAVITSKY, K;BARSHIRA, A;SHILOH, Y
通过定位克隆，在染色体11 q22 -23上鉴定了常染色体隐性遗传性共济失调毛细血管扩张症（AT）中突变的基因ATM。AT的特征在于小脑变性、免疫缺陷、染色体不稳定、癌症易感性、辐射敏感性和细胞周期异常。这种疾病在遗传上是异质的，有四个互补组被怀疑代表不同的基因。ATM具有12种酶的转录物，发现在所有互补组的AT患者中发生突变，表明它可能是导致这种疾病的唯一基因。一个5.9个腺苷酸酶的部分ATM互补DNA克隆编码一种推定的蛋白质，该蛋白质类似于参与有丝分裂信号转导、减数分裂重组和细胞周期控制的几种酵母和哺乳动物磷脂酰肌醇-3 '激酶。ATM的发现应该增强对AT和相关综合征的理解，并可能允许识别AT杂合子，这些杂合子患癌症的风险增加。
A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease is genetically heterogeneous, with four complementation groups that have been suspected to represent different genes. ATM, which has a transcript of 12 kilobases, was found to be mutated in AT patients from all complementation groups, indicating that it is probably the sole gene responsible for this disorder. A partial ATM complementary DNA clone of 5.9 kilobases encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. The discovery of ATM should enhance understanding of AT and related syndromes and may allow the identification of AT heterozygotes, who are at increased risk of cancer.