The RAG1-RAG2 recombinase (RAG) cleaves DNA to initiate V(D)J recombination, but RAG also belongs to the RNH-type transposase family. To learn how RAG-catalyzed transposition is inhibited in developing lymphocytes, we determined the structure of a DNA-strand transfer complex of mouse RAG at 3.1-Å resolution. The target DNA is a T form (T for transpositional target), which contains two >80° kinks towards the minor groove, only 3 bp apart. RAG2, a late evolutionary addition in V(D)J recombination, appears to enforce the sharp kinks and additional inter-segment twisting in target DNA and thus attenuates unwanted transposition. In contrast to strand transfer complexes of genuine transposases, where severe kinks occur at the integration sites of target DNA and thus prevent the reverse reaction, the sharp kink with RAG is 1 bp away from the integration site. As a result, RAG efficiently catalyzes the disintegration reaction that restores the RSS (donor) and target DNA.

中文翻译：

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小鼠 RAG 重组酶如何避免 DNA 转座。

RAG1-RAG2 重组酶 (RAG) 切割 DNA 以启动 V(D)J 重组，但 RAG 也属于 RNH 型转座酶家族。为了了解 RAG 催化的转座如何在发育中的淋巴细胞中受到抑制，我们以 3.1-Å 分辨率确定了小鼠 RAG 的 DNA 链转移复合物的结构。靶 DNA 是 T 型（T 表示转座靶），它包含两个朝向小沟的 >80° 扭结，仅相距 3 bp。RAG2 是 V(D)J 重组中的一种晚期进化添加物，似乎可以增强目标 DNA 中的尖锐扭结和额外的节间扭曲，从而减弱不需要的转座。与真正的转座酶的链转移复合物相比，在目标 DNA 的整合位点会发生严重的扭结，从而阻止逆反应，与 RAG 的尖锐扭结距离集成站点 1 bp。因此，RAG 有效地催化了恢复 RSS（供体）和靶 DNA 的分解反应。