Max Perutz实验室Joao Matos小组揭示了Holliday连接-ZMM蛋白反馈使减数分裂交叉保证。该项研究成果发表在2025年9月24日出版的《自然》上。

在此，该团队在出芽酵母中建立了一个实验系统，使HJs在减数分裂染色体突触建立后能够有条件地进行核分解。课题组发现HJ分解触发突触复合体的完全解体，而不破坏染色体的轴环组织。从机制上讲，HJs介导了ZMM蛋白与同源染色体对轴界面上形成的重组结节的持续结合。ZMM蛋白反过来促进突触复合体的聚合，同时保护HJs不受非交叉途径的加工。ZMM稳定HJs，而HJs在未来的交叉位点保留ZMM蛋白，它们之间的相互反馈维持染色体突触，直到HJ分解酶在退出前期I时被激活。值得注意的是，通过聚合和维持突触复合体结构，HJ-ZMM相互作用抑制从头双链断裂形成和重组再启动。这样，这种相互作用抑制了DNA损伤反应，使减数分裂过程没有未修复的断裂，并支持交叉保证。

据悉，Holliday结（HJs）是在双链断裂修复过程中连接重组染色体的DNA结构分支。尽管存在染色体分离的风险，但HJs在减数分裂前期作为杂交过程中的中间体积累。hj是否具有额外的调节功能尚不清楚。

附：英文原文

Title: Holliday junction–ZMM protein feedback enables meiotic crossover assurance

Author: Henggeler, Adrian, Orli, Lucija, Velikov, Daniel, Matos, Joao

Issue&Volume: 2025-09-24

Abstract: Holliday junctions (HJs) are branched four-way DNA structures that link recombining chromosomes during double-strand break repair1. Despite posing a risk to chromosome segregation, HJs accumulate during meiotic prophase I as intermediates in the process of crossing-over2,3. Whether HJs have additional regulatory functions remains unclear. Here we establish an experimental system in budding yeast that enables conditional nucleolytic resolution of HJs after the establishment of meiotic chromosome synapsis. We find that HJ resolution triggers complete disassembly of the synaptonemal complex without disrupting the axis–loop organization of chromosomes. Mechanistically, HJs mediate the continued association of ZMM proteins with recombination nodules that form at the axes interface of homologous chromosome pairs. ZMM proteins, in turn, promote polymerization of the synaptonemal complex while simultaneously protecting HJs from processing by non-crossover pathways. Thus, reciprocal feedback between ZMMs, which stabilize HJs, and HJs, which retain ZMM proteins at future crossover sites, maintains chromosome synapsis until HJ-resolving enzymes are activated during exit from prophase I. Notably, by polymerizing and maintaining the synaptonemal complex structure, the HJ–ZMM interplay suppresses de novo double-strand break formation and recombination reinitiation. In doing so, this interplay suppresses the DNA damage response, enabling meiotic progression without unrepaired breaks and supporting crossover assurance.

DOI: 10.1038/s41586-025-09559-x

Source: https://www.nature.com/articles/s41586-025-09559-x