MRN復合物是由三個蛋白質(zhì)組成的基因修復復合體,，這個復合體包括MRE11、Nbs1,、Rad50三種蛋白質(zhì),。MRN復合物在DNA雙鏈損傷修復、同源重組、非同源重組,、端粒長度維持,、細胞檢驗點激活、保證DNA復制的順利進行,以及維持基因組的穩(wěn)定性等方面都起到了重要的作用,。
當MRN復合物中的Mre11蛋白缺失時,，會造成B細胞中DNA斷裂修復機制出現(xiàn)錯誤。這一過程稱為抗體類別轉(zhuǎn)換重組（immunoglobulin class switch recombination）,。DNA修復錯誤會改變B細胞功能,，分泌不同抗體抵御病原體入侵機體?？贵w類別轉(zhuǎn)換重組在免疫系統(tǒng)清除病原體時起到重要作用,，但是同樣可能引起細胞癌變。
最近研究人員通過使用只有B細胞內(nèi)Mre11基因突變的小鼠作為模型,，發(fā)現(xiàn)Mre11基因缺陷會使染色體破壞,，當DNA破壞位置處于免疫球蛋白基因里面時，抗體類別轉(zhuǎn)換重組現(xiàn)象會出現(xiàn),。實驗證明Mre11基因與DNA損傷修復有重要聯(lián)系,，而且可能在癌癥預防方面也有關鍵作用。免疫球蛋白基因斷裂后,，可能會與基因組中遠端基因重組,，導致染色體易位造成癌癥。Mre11基因保持正?；钚詴r可以使B細胞DNA雙鏈斷裂得到有效修復,，保證免疫系統(tǒng)正常工作。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Structural & Molecular Biology 16, 808 - 813 (2009) 26 July 2009 | doi:10.1038/nsmb.1639
Multiple functions of MRN in end-joining pathways during isotype class switching
Maria Dinkelmann1,3, Elizabeth Spehalski1,3, Trina Stoneham1, Jeffrey Buis1, Yipin Wu1, JoAnn M Sekiguchi2 & David O Ferguson1
The Mre11–Rad50–NBS1 (MRN) complex has many roles in response to DNA double-strand breaks, but its functions in repair by nonhomologous end joining (NHEJ) pathways are poorly understood. We have investigated requirements for MRN in class switch recombination (CSR), a programmed DNA rearrangement in B lymphocytes that requires NHEJ. To this end, we have engineered mice that lack the entire MRN complex in B lymphocytes or that possess an intact complex that harbors mutant Mre11 lacking DNA nuclease activities. MRN deficiency confers a strong defect in CSR, affecting both the classic and the alternative NHEJ pathways. In contrast, absence of Mre11 nuclease activities causes a milder phenotype, revealing a separation of function within the complex. We propose a model in which MRN stabilizes distant breaks and processes DNA termini to facilitate repair by both the classical and alternative NHEJ pathways.
1 Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
2 Departments of Internal Medicine and Human Genetics, The University of Michigan, Ann Arbor, Michigan, USA.
3 These authors contributed equally to this work.
