Dual role of RAG2 in V(D)J recombination: catalysis and regulation of ordered Ig gene assembly
Dual role of RAG2 in V(D)J recombination: catalysis and regulation of ordered Ig gene assembly
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DOI：
10.1093/emboj/17.16.4881
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发表时间：
1998-08-17
期刊：
影响因子：
11.4
通讯作者：
Oettinger, MA
中科院分区：
文献类型：
--
作者：
Kirch, SA;Rathbun, GA;Oettinger, MA
免疫球蛋白基因在淋巴发育过程中通过一系列位点特异性重排进行组装，这些重排受到严格调控，以确保 B（而非 T）细胞中产生功能性抗体，并且每个细胞上都存在独特的受体。由于包含 RAG1 和 RAG2 蛋白的常见 V(D)J 重组酶用于 B 和 T 细胞抗原受体组装，因此谱系特异性重排必须通过重组位点的不同访问来调节。我们在此表明，RAG2 蛋白的 C 末端虽然对于基本重组反应和 Ig 重链 Du 至 JH 连接是可有可无的，但对于 IgH 处有效的 V-H 至 DJ(H) 重排至关重要因此，RAG2 蛋白在 V(D)J 重组中发挥双重作用，既催化反应又控制进入特定基因座。
Immunoglobulin genes are assembled during lymphoid development by a series of site-specific rearrangements that are tightly regulated to ensure that functional antibodies are generated in B (but not T) cells and that a unique receptor is present on each cell. Because a common V(D)J recombinase comprising RAG1 and RAG2 proteins is used for both B- and T-cell antigen receptor assembly, lineage-specific rearrangement must be modulated through differential access to sites of recombination, We show here that the C-terminus of the RAG2 protein, although dispensable for the basic recombination reaction and for Ig heavy chain Du to JH joining, is essential for efficient V-H to DJ(H) rearrangement at the IgH locus, Thus, the RAG2 protein plays a dual role in V(D)J recombination, acting both in catalysis of the reaction and in governing access to particular loci.