Abstract
Meiotic recombination ensures genetic diversity and accurate chromosome segregation by mediating reciprocal DNA exchange between homologous chromosomes. In this process, the meiosis-specific recombinase DMC1 plays a pivotal role in homology search and pairing, but the molecular mechanisms underlying its function remain unclear. Using single-molecule imaging, we demonstrate that the human DMC1-ssDNA presynaptic complex employs a diffusion-based mechanism to search for homologous DNA. Although this diffusing complex generates a migrating DNA "bubble," it cannot align with the homologous sequence in the absence of free DMC1 protein. Strikingly, the meiosis-specific cofactor complex HOP2-MND1 compensates for the lack of free DMC1 and enables homology recognition. Notably, HOP2-MND1 achieves this by codiffusing with the presynaptic complex, acting to clamp the ssDNA-dsDNA junctions and maintain an expanded DNA bubble conducive to sequence alignment. Our findings identify DMC1 together with HOP2-MND1 as a functional homology search unit and provide mechanistic insights into how auxiliary factors regulate DMC1-driven strand exchange during meiotic recombination.