Model of how Smc5/6-Mms21 may antagonize inappropriate JMs in meiotic recombination.

<p>(A) A representation of homologous recombination and intermediate pathway choice in the course of budding yeast meiosis is shown, along with the points of function for Smc5/6-Mms21 in antagonizing inappropriate JMs. Meiotic DSBs can engage for two alternative fates: non-ZMM DSBs and ZMM-DSBs (highlighted in green). Regular pathway progression is marked with blue arrows and aberrant deviations are depicted in red. By default, stable strand invasions are disassembled for all breaks through the action of Sgs1 helicase and Smc5/6-Mms21. Non-ZMM DSBs are consequently repaired by SDSA into non-crossovers. In contrast, ZMM-DSBs are in addition also prevented from being repaired at all until licensed in the ZMM pathway for progression to stable invasions, here referred to as “ZMM-Repair Barrier”. When a ZMM-DSB is allowed to form stable SEIs and dHJs, the ZMM-pathway protects that DSB from the action of Sgs1 and Smc5/6-Mms21 and marks the resulting dHJ for CO specific resolution by Exo1-Mlh1/3. Intermediates that deviate from their supposed repair pathways by inappropriate intermediate stabilization and absence of a ZMM label result in “rogue” JMs that depend on Smc5/6-Mms21 for resolution by the rogue JM resolvase Mus81-Mms4 (and probably also Slx1-Slx4 and Yen1). (B) Our data implicates the Smc5/6-Mms21 complex in at least two independent mechanisms for rogue JM avoidance: On one hand prevention of JM formation through Mms21 SUMO E3 mediated regulation of anti-recombinogenic helicases, and on the other hand, the promotion of resolution of JMs by rogue JM resolvases. We also assume that through regulation of helicases, the Smc5/6-Mms21 complex may very likely also be involved in regulating dHJ dissolution by Sgs1-Rmi1-Top3. (C) Smc5/6-Mms21 may survey the DNA for displaced ssDNA at D-loops or HJs by topologically entrapping dsDNA as a sliding SMC ring and binding stably to ssDNA (e.g. at the hinge or any other part of the ring) upon encounter. Stable binding to such ssDNA will constrain D-loop extension and HJ branch migration and label sites with a ssDNA/dsDNA interface where appropriate action of anti-recombinogenic helicases (like Sgs1 or Mph1) and resolvases will be required.