生物谷报道： 一项新的研究显示，一种早就知道与保护细胞不发生基因损伤的蛋白质的保护能力被低估。研究显示，这种蛋白质甚至在保护细胞后代方面具有更为重要的功能。
这项由美国洛克菲勒大学、霍华德休斯医学院和美国癌症研究院研究人员组成的研究队伍证实，这种叫做ATM的蛋白质不但对免疫细胞DNA双链缺口的修复至关重要，而且还是防止基因损伤被传递给后代细胞过程中起到一定的作用。
在B淋巴细胞生命周期的初期阶段，它们重排DNA，从而形成不同的表面受体，即V(D)J重组，而这种受体能识别不同的入侵者。现在，洛克菲勒的Michel Nussenzweig教授与霍华德休斯等研究机构的研究人员合作进行的这项研究表明，当ATM蛋白质缺失时，在V(D)J重组过程中形成的染色体缺口就无法被修复，并且通常能阻止受损细胞进行复制的检查点（checkpoint）也丧失了。这项研究的结果发表在最新一期的Cell杂志上。
研究人员发现ATM蛋白质似乎在B细胞中有两个功能：帮助修复DNA双链缺口；活化细胞周期检查点。研究人员解释说，已经知道ATM是B细胞知晓自己是否有缺口染色体所必须的，但是之前并不知道它还能继续起作用。
由于ATM蛋白质在一些淋巴瘤中发生了突变，因此这项新的发现暗示研究人员，淋巴细胞可能在很长的时间里携带DNA损伤，并且这种损伤可能在之后染色体迁移、遗传物质重组过程产生一定的影响，从而可能导致癌症的发生。
英文原文：http://www.physorg.com/news102337637.html
原始出处:
10.1016/j.cell.2007.06.016
ATM Prevents the Persistence and Propagation of Chromosome Breaks in Lymphocytes
Elsa Callén,1 Mila Jankovic,2 Simone Difilippantonio,1 Jeremy A. Daniel,1 Hua-Tang Chen,1 Arkady Celeste,1 Manuela Pellegrini,1 Kevin McBride,2 Danny Wangsa,3 Andrea L. Bredemeyer,4 Barry P. Sleckman,4 Thomas Ried,3 Michel Nussenzweig,2,5, and André Nussenzweig1,5,
1 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA
2 Laboratory of Molecular Immunology, The Rockefeller University, and Howard Hughes Medical Institute, New York, NY 10021, USA
3 Section of Cancer Genomics, Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
4 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Corresponding author
André Nussenzweig
andre_nussenzweig@nih.gov
Corresponding author
Michel Nussenzweig
nussen@mail.rockefeller.edu
DNA double-strand breaks (DSBs) induce a signal transmitted by the ataxia-telangiectasia mutated (ATM) kinase, which suppresses illegitimate joining of DSBs and activates cell-cycle checkpoints. Here we show that a significant fraction of mature ATM-deficient lymphocytes contain telomere-deleted ends produced by failed end joining during V(D)J recombination. These RAG-1/2 endonuclease-dependent, terminally deleted chromosomes persist in peripheral lymphocytes for at least 2 weeks in vivo and are stable over several generations in vitro. Restoration of ATM kinase activity in mature lymphocytes that have transiently lost ATM function leads to loss of cells with terminally deleted chromosomes. Thus, maintenance of genomic stability in lymphocytes requires faithful end joining as well a checkpoint that prevents the long-term persistence and transmission of DSBs. Silencing this checkpoint permits DNA ends produced by V(D)J recombination in a lymphoid precursor to serve as substrates for translocations with chromosomes subsequently damaged by other means in mature cells.
