Perkins Eric J, Nair Ayyappan, Cowley Dale O, Van Dyke Terry, Chang Yung, Ramsden Dale A
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Genes Dev. 2002 Jan 15;16(2):159-64. doi: 10.1101/gad.956902.
Ataxia-telangiectasia mutated (ATM) is required for resistance to radiation-induced DNA breaks. Here we use chromatin immunoprecipitation to show that ATM also localizes to breaks associated with V(D)J recombination. ATM recruitment to the recombining locus correlates approximately with recruitment of the break-initiating factor RAG1 and precedes efficient break repair, consistent with localization of ATM to normal recombination intermediates. A product of ATM kinase activity, Ser 18-phosphorylated p53, was detected similarly at these breaks, arguing that ATM phosphorylates target proteins in situ. We suggest routine surveillance of intermediates in V(D)J recombination by ATM helps suppress potentially oncogenic translocations when repair fails.
共济失调毛细血管扩张症突变基因（ATM）对于抵抗辐射诱导的DNA断裂是必需的。在此我们利用染色质免疫沉淀法表明，ATM也定位于与V（D）J重组相关的断裂处。ATM募集到重组位点与断裂起始因子RAG1的募集大致相关，且先于有效的断裂修复，这与ATM定位于正常重组中间体一致。在这些断裂处同样检测到ATM激酶活性的产物——丝氨酸18磷酸化的p53，这表明ATM在原位磷酸化靶蛋白。我们认为，当修复失败时，ATM对V（D）J重组中间体进行常规监测有助于抑制潜在的致癌性易位。
