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由RAG1和RAG2蛋白介导的DNA转座:致癌易位的一个可能来源。

DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations.

作者信息

Hiom K, Melek M, Gellert M

机构信息

Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.

出版信息

Cell. 1998 Aug 21;94(4):463-70. doi: 10.1016/s0092-8674(00)81587-1.

DOI:10.1016/s0092-8674(00)81587-1
PMID:9727489
Abstract

The RAG1 and RAG2 proteins are known to initiate V(D)J recombination by making a double-strand break between the recombination signal sequence (RSS) and the neighboring coding DNA. We show that these proteins can also drive the coupled insertion of cleaved recombination signals into new DNA sites in a transpositional reaction. This RAG-mediated DNA transfer provides strong evidence for the evolution of the V(D)J recombination system from an ancient mobile DNA element and suggests that repeated transposition may have promoted the expansion of the antigen receptor loci. The inappropriate diversion of V(D)J rearrangement to a transpositional pathway may also help to explain certain types of DNA translocation associated with lymphatic tumors.

摘要

已知RAG1和RAG2蛋白通过在重组信号序列(RSS)和相邻的编码DNA之间产生双链断裂来启动V(D)J重组。我们发现,这些蛋白还能在转座反应中驱动切割后的重组信号插入到新的DNA位点。这种由RAG介导的DNA转移为V(D)J重组系统从古老的可移动DNA元件进化而来提供了有力证据,并表明重复转座可能促进了抗原受体基因座的扩增。V(D)J重排不恰当地转向转座途径也可能有助于解释与淋巴瘤相关的某些类型的DNA易位。

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