SYCP2 recruits HORMAD2 to chromosome axes for unsynapsed chromatin silencing and synapsis surveillance in meiosis.

Faithful chromosome segregation during meiosis requires accurate recombination and synapsis of homologous chromosomes. These processes are monitored in mammals by checkpoints involving the meiotic HORMA-domain proteins HORMAD1 and HORMAD2, which bind unsynapsed chromosome axes and promote activation of the DNA damage-response kinase ATR independently of DNA double-strand breaks (DSBs). However, the in vivo mechanism for axial HORMAD1 and HORMAD2 recruitment and its relevance to checkpoint signaling remain unclear, although the chromosome-axis component SYCP2 has been proposed to contain a candidate HORMAD-binding closure motif (CM). We show that deletion of the SYCP2 CM disrupts SYCP2-HORMAD2 complexes and selectively prevents HORMAD2 axis binding without affecting axis assembly, recombination, or axial HORMAD1 recruitment. Consequently, ATR accumulation and signaling on unsynapsed axes are reduced, and the prophase checkpoint malfunctions, manifesting in aberrant elimination of synapsis-proficient spermatocytes and persistence of asynaptic oocytes, which reflect sex-specific characteristics of checkpoint mechanisms. The phenotypes of SYCP2-CM-deficient and HORMAD2-null mice are indistinguishable, establishing the requirement for HORMAD2 axis recruitment in synapsis surveillance. We propose that axial recruitment generates a HORMAD2 scaffold that drives clustering-mediated ATR network activation independently of DSBs, thereby linking chromosome-axis architecture to synapsis quality control in mammalian meiosis.