生物谷報(bào)道： 一項(xiàng)新的研究顯示,，一種早就知道與保護(hù)細(xì)胞不發(fā)生基因損傷的蛋白質(zhì)的保護(hù)能力被低估,。研究顯示，這種蛋白質(zhì)甚至在保護(hù)細(xì)胞后代方面具有更為重要的功能,。
這項(xiàng)由美國洛克菲勒大學(xué),、霍華德休斯醫(yī)學(xué)院和美國癌癥研究院研究人員組成的研究隊(duì)伍證實(shí)，這種叫做ATM的蛋白質(zhì)不但對免疫細(xì)胞DNA雙鏈缺口的修復(fù)至關(guān)重要,，而且還是防止基因損傷被傳遞給后代細(xì)胞過程中起到一定的作用,。
在B淋巴細(xì)胞生命周期的初期階段，它們重排DNA,，從而形成不同的表面受體,，即V(D)J重組，而這種受體能識別不同的入侵者?，F(xiàn)在,，洛克菲勒的Michel Nussenzweig教授與霍華德休斯等研究機(jī)構(gòu)的研究人員合作進(jìn)行的這項(xiàng)研究表明，當(dāng)ATM蛋白質(zhì)缺失時(shí),，在V(D)J重組過程中形成的染色體缺口就無法被修復(fù),，并且通常能阻止受損細(xì)胞進(jìn)行復(fù)制的檢查點(diǎn)（checkpoint）也喪失了。這項(xiàng)研究的結(jié)果發(fā)表在最新一期的Cell雜志上,。
研究人員發(fā)現(xiàn)ATM蛋白質(zhì)似乎在B細(xì)胞中有兩個(gè)功能：幫助修復(fù)DNA雙鏈缺口,；活化細(xì)胞周期檢查點(diǎn)。研究人員解釋說,，已經(jīng)知道ATM是B細(xì)胞知曉自己是否有缺口染色體所必須的,，但是之前并不知道它還能繼續(xù)起作用。
由于ATM蛋白質(zhì)在一些淋巴瘤中發(fā)生了突變,，因此這項(xiàng)新的發(fā)現(xiàn)暗示研究人員,，淋巴細(xì)胞可能在很長的時(shí)間里攜帶DNA損傷，并且這種損傷可能在之后染色體遷移,、遺傳物質(zhì)重組過程產(chǎn)生一定的影響,，從而可能導(dǎo)致癌癥的發(fā)生。
英文原文：http://www.physorg.com/news102337637.html
原始出處:
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
[email protected]
Corresponding author
Michel Nussenzweig
[email protected]
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.
