Jeggo P A, Carr A M, Lehmann A R
MRC Cell Mutation Unit, University of Sussex, Brighton, UK.
Trends Genet. 1998 Aug;14(8):312-6. doi: 10.1016/s0168-9525(98)01511-x.
Ataxia-telangiectasia (A-T) is an autosomal recessive human disorder that, because of its multisystem nature, is of interest to scientists and clinicians from many disciplines. A-T patients have defects in the neurological and immune systems, telangiectasia in the eyes and face, and are, in addition, cancer-prone and radiation-sensitive. A-T cell lines have a range of diverse phenotypes including sensitivity to ionizing radiation and defects in cell-cycle checkpoint control. The ATM protein is a member of the PI 3-kinase-like superfamily, and it has been widely accepted that A-T cells represent mammalian cell-cycle checkpoint mutants and that the radiation sensitivity is a consequence of this defect. However, several lines of evidence suggest that A-T cells have distinct repair and checkpoint defects. A-T cells therefore appear to harbour dual checkpoint/repair defects. Here, we review the evidence supporting this contention and consider its implications for an analysis of the A-T phenotype.
共济失调毛细血管扩张症（A-T）是一种常染色体隐性人类疾病，因其多系统性质，受到来自许多学科的科学家和临床医生的关注。A-T患者存在神经和免疫系统缺陷、眼睛和面部毛细血管扩张，此外还易患癌症且对辐射敏感。A-T细胞系具有一系列不同的表型，包括对电离辐射敏感和细胞周期检查点控制缺陷。ATM蛋白是PI 3激酶样超家族的成员，人们普遍认为A-T细胞代表哺乳动物细胞周期检查点突变体，辐射敏感性是这种缺陷的结果。然而，几条证据表明A-T细胞具有独特的修复和检查点缺陷。因此，A-T细胞似乎存在双重检查点/修复缺陷。在这里，我们回顾支持这一论点的证据，并考虑其对A-T表型分析的影响。
