Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
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DOI：
10.1038/29457
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发表时间：
1998-08-20
期刊：
影响因子：
64.8
通讯作者：
Schatz, DG
中科院分区：
文献类型：
--
作者：
Agrawal, A;Eastman, QM;Schatz, DG
免疫球蛋白和T细胞受体基因通过位点特异性重组反应（V（D）J重组）由发育中的淋巴细胞中的组分基因片段组装而成。重组激活基因RAG 1和RAG 2编码的蛋白质在该反应中是必需的，介导明确定义的重组信号的序列特异性DNA识别和这些信号旁边的DNA切割。在这里，我们表明，RAG1和RAG2一起形成一个转座酶，能够切除一段含有重组信号的DNA从供体位点，并将其插入到一个目标DNA分子。所形成的产物含有直接位于转座片段侧翼的靶DNA的短重复，该结构类似于逆转录病毒整合和所有已知转座反应所产生的结构。这些结果支持了这样的理论，即RAG1和RAG2曾经是转座因子的组成部分，并且免疫球蛋白和T细胞受体基因的分裂性质来自于在有颌和无颌脊椎动物进化分歧后不久将该因子插入祖先受体基因的种系。
Immunoglobulin and T-cell-receptor genes are assembled from component gene segments in developing lymphocytes by a site-specific recombination reaction, V(D)J recombination, The proteins encoded by the recombination-activating genes, RAG1 and RAG2, are essential in this reaction, mediating sequence-specific DNA recognition of well-defined recombination signals and DNA cleavage next to these signals. Here we show that RAG1 and RAG2 together form a transposase capable of excising a piece of DNA containing recombination signals from a donor site and inserting it into a target DNA molecule. The products formed contain a short duplication of target DNA Immediately flanking the transposed fragment, a structure like that created by retroviral integration and all known transposition reactions. The results support the theory that RAG1 and RAG2 were once components of a transposable element, and that the split nature of Immunoglobulin and T-cell-receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates.