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Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system (see comments)

机译:RAG1和RAG2介导的转座及其对免疫系统进化的影响(请参阅评论)

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摘要

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.
机译:免疫球蛋白和T细胞受体基因是通过位点特异性重组反应(V(D)J重组)从发育中的淋巴细胞中的组成基因片段组装而成的。由重组激活基因RAG1和RAG2编码的蛋白质在此反应中至关重要,介导明确定义的重组信号的序列特异性DNA识别以及紧接这些信号的DNA裂解。在这里,我们显示RAG1和RAG2一起形成一个转座酶,能够从供体位点切除包含重组信号的DNA片段并将其插入目标DNA分子中。所形成的产物包含目标DNA的短重复,该DNA紧邻转座片段,其结构类似于逆转录病毒整合和所有已知的转座反应所产生的结构。结果支持以下理论:RAG1和RAG2曾经是可转座元件的组成部分,并且免疫球蛋白和T细胞受体基因的分裂性质源自该种的进化分化后不久将该元件的种系插入祖先受体基因中和无颚的脊椎动物。

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