Petrini J H
University of Wisconsin Medical School, Madison, WI 53706, USA.
Curr Opin Cell Biol. 2000 Jun;12(3):293-6. doi: 10.1016/s0955-0674(00)00091-0.
Recently, findings regarding a group of cancer predisposition and chromosome instability syndromes, Nijmegen breakage syndrome (NBS), the ataxia-telangiectasia-like disorder (A-TLD) and ataxia telangiectasia have shed light on the unexpected role of recombinational DNA repair proteins in DNA-damage-dependent cell-cycle regulation. Mutations in the Mre11 complex cause A-TLD and NBS. In addition, functions of the Mre11 complex have been biochemically linked to ATM, the large protein kinase that is defective in ataxia-telangiectasia cells by the observation that Nbs1 is a bona fide substrate of the ATM kinase.
最近,关于一组癌症易感性和染色体不稳定综合征,即尼曼匹克氏症(NBS)、共济失调毛细血管扩张样疾病(A-TLD)和共济失调毛细血管扩张症的研究结果,揭示了重组DNA修复蛋白在依赖DNA损伤的细胞周期调控中出人意料的作用。Mre11复合物中的突变会导致A-TLD和NBS。此外,通过观察发现Nbs1是ATM激酶的真正底物,Mre11复合物的功能在生化上与ATM相关联,ATM是一种大型蛋白激酶,在共济失调毛细血管扩张症细胞中存在缺陷。