Dimerization of the S. cerevisiae Spo11 core complex
Spo11 initiates meiotic recombination by introducing programmed DNA double-strand breaks. DNA cleavage occurs via a topoisomerase-like mechanism involving hybrid active sites formed at the dimer interface. However, in contrast to its topoisomerase relative (Topo VI), Spo11 does not form a stable dimer, likely to prevent uncontrolled DNA cleavage. Here, we investigated the dimerization of S. cerevisiae Spo11 in complex with its partners Ski8, Rec102, and Rec104. We show that the Spo11 complex dimerizes transiently on DNA, forming unstable dimeric complexes with duplex and branched DNA substrates. Guided by AlphaFold modeling of a pre-cleavage complex, we identified mutations that reduce dimerization. Surprisingly, DSB formation is resilient to mutagenesis of the Spo11 dimer interface, implying that additional factors promote dimerization in vivo. Finally, we found that Rec102 exerts a key DNA-binding function, essential for catalysis, and show that it also participates in dimerization through trans contacts with Ski8. Our work provides new insights into the mechanism of Spo11 dimerization and the role of its partners in initiating meiotic recombination.