Increased radiosensitivity and the basic defect in ataxia telangiectasia.
Increased radiosensitivity and the basic defect in ataxia telangiectasia.
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放射敏感性增加和共济失调毛细血管扩张的基本缺陷。
DOI：
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发表时间：
1989
影响因子：
2.6
通讯作者：
C. McConville
中科院分区：
文献类型：
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作者：
A. Taylor;J. Metcalfe;C. McConville
在共济失调毛细血管扩张（A-T）细胞中已经发现了各种细胞缺陷，包括增加的放射敏感性、增加的对各种化学试剂的敏感性、可能的DNA修复缺陷和DNA合成缺陷。这些不同的特征是如何相互联系的，目前还不清楚。有人认为，有一个缺陷，在A-T的组织分化，以及在生长和成熟的成年人。这一假说得到了观察结果的支持，例如，患者中存在不成熟的胸腺，甲胎蛋白的产生导致高血清水平，以及卵巢发育不全。A-T基因最近被定位于染色体区域11 q22 -23，这是一些非淋巴白血病中涉及染色体易位的位点。在染色体水平上，A-T的自发异常包括：第一，表现出染色体易位的细胞频率增加，涉及免疫系统基因，这些基因通常经历重排以形成功能产物;第二，在淋巴细胞和成纤维细胞中形成端粒双着丝粒;第三，在暴露于电离辐射和拟放射性药物后形成长寿命的染色体损伤。这种疾病背后的基因缺陷是未知的，区分突变基因的原发性和继发性影响是困难的。我们考虑保留易位T细胞的替代模型。第一，可能是识别位点特异性损伤的缺陷导致易位细胞的保留，否则这些细胞可能会被去除。第二，一个共同的特点，生产非法的T细胞受体基因重排和端粒双着丝粒染色体在A-T细胞的形成是一个增加的时间段可用于染色体互换，可能是由于在链断裂修复的位点特异性缺陷。这种缺陷也可能阻止细胞暴露于电离辐射后的染色体恢复。
Various cellular defects have been found in ataxia telangiectasia (A-T) cells including increased radiosensitivity, increased sensitivity to various chemical agents, a probable DNA repair defect and a defect in DNA synthesis. How these different features are related to each other is at present unknown. It has been suggested that there is a defect in A-T that acts in tissue differentiation as well as during growth and in the mature adult. This hypothesis is supported by the observations, for example, of an immature thymus present in patients, the production of alpha-fetoprotein, which results in a high serum level, and ovarian dysgenesis. A gene for A-T has recently been localized to chromosome region 11q22-23, a site involved in chromosomes translocations in some non-lymphoid leukaemias. At the chromosomal level the spontaneous abnormalities in A-T include, first, an increased frequency of cells showing chromosome translocations involving immune system genes that normally undergo rearrangement to form a functional product; secondly, the formation of telometric dicentrics in both lymphocytes and fibroblasts; and thirdly formation of long-lived chromosome damage following exposure to ionizing radiation and radiomimetic drugs. The gene defect underlying this disorder is unknown and distinguishing between primary and secondary effects of the mutant gene is difficult. We consider alternative models for retention of translocation T cells. First, it is possible that there is a defect in recognition of site-specific damage leading to retention of translocation cells that might otherwise be removed. Secondly, a feature common to the production of illegitimate T-cell receptor gene rearrangements and to formation of telomeric dicentric chromosomes in A-T cells is an increased period of time available for chromosome interchange, possibly due to a site-specific defect in strand break repair. It is possible that this defect may also prevent chromosome restitution following exposure of cells to ionizing radiation.
影响因子：
56.9
作者：
CORNFORTH, MN;BEDFORD, JS
通讯作者：
BEDFORD, JS