Evidence for Ku70/Ku80 association with full-length RAG1
Evidence for Ku70/Ku80 association with full-length RAG1
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DOI：
10.1093/nar/gkn049
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发表时间：
2008-04-01
影响因子：
14.9
通讯作者：
Swanson, Patrick C.
中科院分区：
文献类型：
--
作者：
Rval, Prafulla;Kriatchko, Aleksei N.;Swanson, Patrick C.
抗原受体基因通过称为V（D）J重组的位点特异性DNA重排过程组装。该过程通过两个不同的阶段进行：切割阶段，其中RAG1和RAG2蛋白在抗原受体基因片段处引入DNA双链断裂，以及连接阶段，其中所产生的DNA断裂通过非同源末端连接（NHEJ）修复途径进行处理和修复。遗传和生物化学证据表明，RAG蛋白在指导V（D）J重组至NHEJ途径期间引入的DNA断裂的修复中发挥积极作用。然而，RAG蛋白和NHEJ中涉及的任何因子之间的特异性关联的证据仍然难以捉摸。在这里，我们提出的证据表明，NHEJ途径的两个组成部分，Ku70和Ku80，与全长RAG1相互作用，提供了V（D）J重组的两个阶段之间的生化联系。
Antigen receptor genes are assembled by a site-specific DNA rearrangement process called V(D)J recombination. This process proceeds through two distinct phases: a cleavage phase in which the RAG1 and RAG2 proteins introduce DNA double-strand breaks at antigen receptor gene segments, and a joining phase in which the resulting DNA breaks are processed and repaired via the non-homologous end-joining (NHEJ) repair pathway. Genetic and biochemical evidence suggest that the RAG proteins play an active role in guiding the repair of DNA breaks introduced during V(D)J recombination to the NHEJ pathway. However, evidence for specific association between the RAG proteins and any of the factors involved in NHEJ remains elusive. Here we present evidence that two components of the NHEJ pathway, Ku70 and Ku80, interact with full-length RAG1, providing a biochemical link between the two phases of V(D)J recombination.