CHARACTERIZATION OF THE ATAXIA-TELANGIECTASIA GENE PRODUCT

共济失调-毛细血管扩张症是一种常染色体隐性遗传疾病 以眼皮肤毛细血管扩张和进行性 神经运动功能障碍，细胞和体液免疫缺陷， 对电离辐射过敏， 白血病和淋巴瘤。ATM基因由一个13 kb的转录本组成 编码3056个氨基酸的蛋白质，并在酵母中显示同源性， 果蝇和其他哺乳动物的催化亚基 参与细胞周期调控的磷脂酰肌醇-3激酶 进展和细胞对DNA损伤的反应。功能研究 酵母同源物TEL 1和MEC 1的突变表明， 基因引起的细胞特征与在A-T中观察到的相似 细胞类似地，小鼠Atm基因已经通过基因突变被破坏。 面向. Atm等位基因缺陷的纯合子小鼠显示生长 发育迟缓，神经功能障碍， 形成成熟的配子，T淋巴细胞成熟缺陷和极端 对伽马射线的敏感性。使用为ATM开发的Ab 蛋白我们的额外发现表明ATM蛋白是 只存在于成纤维细胞的细胞核中， 蛋白质与微粒体的额外共分级分离， ATM蛋白仍然是核蛋白， 在细胞周期的所有阶段， 成纤维细胞; ATM蛋白表达不被诱导 与p53不同的γ辐射。

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by oculocutaneous telangiectasias and progressive neuromotor dysfunction, cellular and humoral immune deficiencies, hypersensitivity to ionizing radiation and increased predisposition to leukemias and lymphomas. TheATM gene consists of a 13 kb transcript encoding a 3056 amino acid protein and shows homology in yeast, Drosophila , and other mammals to the catalytic subunit of phosphatidylinositol-3 kinase involved in the control of cell cycle progression and in cellular responses to DNA damage. Functional studies on the yeast homologs, TEL1 and MEC1, indicate that mutations in these genes give rise to cellular features similar to those observed in A-T cells. Similarly, the mouse Atm gene has been disrupted via gene targeting. Homozygous mice deficient in the Atm allele displayed growth retardation, neurologic dysfunction, infertility arising from failure to form mature gametes, defects in T lymphocyte maturation and extreme sensitivity to gamma-irradiation. Using an Ab developed for the ATM protein. Our additional findings indicate that the ATM protein is exclusively found in the nucleus of fibroblast cells and with an additional cofractionation of the protein with microsomes in lymphoblasts; that the ATM protein remains nuclear and not associated with any cellular structures at all stages in the cell cycle in fibroblasts; and the ATM protein expression is not induced by gamma-irradiation unlike that of p53.