Ashley T, Westphal C, Plug-de Maggio A, de Rooij D G
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Cytogenet Genome Res. 2004;107(3-4):256-62. doi: 10.1159/000080603.
ATM, the protein product of the gene mutated in the human autosomal recessive disorder ataxia telangiectasia, is involved in detection of double strand breaks (DSBs) and is a key component of the damage surveillance network of cell cycle proteins. In somatic cells ATM phosphorylates many other proteins including p53, an important regulator of cell cycle control. Mice deficient for Atm are male sterile with arrest and apoptosis occurring at testis epithelial stage IV, which in normal spermatocytes corresponds to mid-pachynema. Unlike the situation in somatic cells, we find no evidence that disruption of the Trp53 (p53) gene, or its down-stream target Cdkn1a (p21/Cip1) results in even a partial rescue of the Atm defect.
ATM是人类常染色体隐性疾病共济失调毛细血管扩张症中发生突变的基因的蛋白质产物，它参与双链断裂（DSB）的检测，并且是细胞周期蛋白损伤监测网络的关键组成部分。在体细胞中，ATM使包括p53（细胞周期控制的重要调节因子）在内的许多其他蛋白质磷酸化。Atm基因缺陷的小鼠雄性不育，在睾丸上皮细胞IV期出现停滞和凋亡，这在正常精母细胞中相当于粗线期中期。与体细胞中的情况不同我们没有发现证据表明Trp53（p53）基因或其下游靶点Cdkn1a（p21/Cip1）的破坏能部分挽救Atm缺陷。
