Nibrin functions in Ig class-switch recombination
Nibrin functions in Ig class-switch recombination
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DOI：
10.1073/pnas.0409191102
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发表时间：
2005-02-01
影响因子：
11.1
通讯作者：
Radbruch, A
中科院分区：
文献类型：
--
作者：
Kracker, S;Bergmann, Y;Radbruch, A
奈梅金氏断裂综合征(NBS)是一种罕见的常染色体隐性遗传病，其特征是易患血液系统恶性肿瘤、细胞周期检查点缺陷和电离辐射敏感性。NBS是由编码nibrin的NBS1基因的亚型突变引起的，它与Well和Rad50形成蛋白质复合体，两者都参与DNA修复。Nibrin定位于类切换的染色体位置，而NBS患者的B细胞在切换重组的位置显示出更多的微同源。由于nibrin对胚胎存活至关重要，因此缺乏通过靶向缺失的方式直接证明nibrin在类交换重组中的作用。在这里，我们通过对NBS1的小鼠同源物NBN的特定细胞类型的条件灭活，表明Nibrin在修复伽玛辐射损伤、维持染色体稳定性以及B淋巴细胞中Ig恒定区基因的重组中发挥作用。
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by predisposition to hematopoietic malignancy, cell-cycle checkpoint defects, and ionizing radiation sensitivity. NBS is caused by a hypomorphic mutation of the NBS1 gene, encoding nibrin, which forms a protein complex with Well and Rad50, both involved in DNA repair. Nibrin localizes to chromosomal sites of class switching, and B cells from NBS patients show an enhanced presence of microhomologies at the sites of switch recombination. Because nibrin is crucial for embryonic survival, direct demonstration by targeted deletion that nibrin functions in class switch recombination has been lacking. Here, we show by cell-type-specific conditional inactivation of Nbn, the murine homologue of NBS1, that nibrin plays a role in the repair of gamma-irradiation damage, maintenance of chromosomal stability, and the recombination of Ig constant region genes in B lymphocytes.