调控桥接重组方向性的结构机制，这一成果由日本东京大学Hiroshi Nishimasu小组经过不懈努力而取得。相关论文发表在2026年8月12日出版的《自然》杂志上。

在这里，该研究组发现bRNA在大肠杆菌基因组的IS621位点弱表达，并且IS621重组酶- bRNA复合物介导的切除效率低于插入效率。

此外，该课题组展示了与切除DNA底物结合的IS621重组酶- bRNA复合物的低温电镜结构，为切除反应提供了机制见解。与先前报道的供体和靶标结合的插入复合体类似，切除复合体包括两个重组酶二聚体，每个都容纳bRNA的靶环和供体结合环。

然而，两种复合物之间的DNA识别明显不同。虽然供体和靶DNA在插入过程中形成弯曲的u形，但切除底物采用线性构象，并在两个bRNA环上结合，形成X形结构。这种几何形状降低了顶链交换的效率，并有助于自然观察到的偏向于插入而不是切除。尽管存在这些差异，但这两种反应的效率相似地通过bRNA中特定二核苷酸（称为握手指南）和DNA底物顶部链之间的碱基配对来调节。总的来说，这项研究提供了完整的IS110换位周期的机制见解，并促进了可编程桥接编辑应用程序的优化设计。

据悉，来自IS110转座子家族的桥接重组酶，如IS621，与桥接RNA （bRNA）结合，介导供体DNA和靶DNA之间的可编程重组。尽管插入是由重组酶- bRNA复合物介导的，但尚不清楚IS621元件如何从宿主基因组中切除以形成转位所需的环状DNA中间体。

附：英文原文

Title: Structural mechanism governing the directionality of bridge recombination

Author: Hiraizumi, Masahiro, Athukoralage, Januka S., Perry, Nicholas T., Tsujimoto, Eisuke, Shiojiri, Nami, Nagahata, Naoto, Lee, Lauren, Sun, Gwanggyu, Durrant, Matthew G., Chandrasekaran, Sita S., Konermann, Silvana, Yamashita, Keitaro, Hsu, Patrick D., Nishimasu, Hiroshi

Issue&Volume: 2026-08-12

Abstract: Bridge recombinases from the IS110 family of transposons, such as IS621, associate with a bridge RNA (bRNA) to mediate programmable recombination between donor DNA and target DNA1,2. Although insertion is mediated by the recombinase–bRNA complex, it remains unknown how IS621 elements are excised from host genomes to form the circular DNA intermediates required for transposition. Here we show that bRNA is weakly expressed from IS621 loci in the Escherichia coli genome and that the IS621 recombinase–bRNA complex mediates excision less efficiently than insertion. Furthermore, we present the cryo-electron microscopy structures of the IS621 recombinase–bRNA complex bound to excision DNA substrates, providing mechanistic insights into the excision reaction. Similar to the previously reported donor- and target-bound insertion complex2, the excision complex comprises two recombinase dimers, each accommodating the target- and donor-binding loops of the bRNA. However, DNA recognition differs notably between the two complexes. Although the donor and target DNAs form a bent U-shape during insertion2, the excision substrates adopt linear conformations and bind across both bRNA loops, forming an X-shaped structure. This geometry reduces the efficiency of top-strand exchange and contributes to the naturally observed bias favouring insertion over excision. Despite these differences, the efficiencies of both reactions are similarly modulated by base pairing between specific dinucleotides in the bRNA, termed handshake guides, and the top strands of the DNA substrates. Overall, this study provides mechanistic insights into the complete IS110 transposition cycle and facilitates the optimal design of programmable bridge-editing applications.

DOI: 10.1038/s41586-026-10903-y

Source: https://www.nature.com/articles/s41586-026-10903-y