Yeast mutants lacking meiotic proteins Zip1, Zip2, Zip3, Mer3, and/or Msh5 (ZMMs) were analyzed for recombination, synaptonemal complex (SC), and meiotic progression. At 33 degrees C, recombination-initiating double-strand breaks (DSBs) and noncrossover products (NCRs) form normally while formation of single-end invasion strand exchange intermediates (SEIs), double Holliday junctions, crossover products (CRs), and SC are coordinately defective. Thus, during wild-type meiosis, recombinational interactions are differentiated into CR and NCR types very early, prior to onset of stable strand exchange and independent of SC. By implication, crossover interference does not require SC formation. We suggest that SC formation may require interference. Subsequently, CR-designated DSBs undergo a tightly coupled, ZMM-promoted transition that yields SEI-containing recombination complexes embedded in patches of SC. zmm mutant phenotypes differ strikingly at 33 degrees C and 23 degrees C, implicating higher temperature as a positive effector of recombination and identifying a checkpoint that monitors local CR-specific events, not SC formation, at late leptotene.

We show that, during budding yeast meiosis, axis ensemble Hop1/Red1 and synaptonemal complex (SC) component Zip1 tend to occur in alternating strongly staining domains. The widely conserved AAA؉-ATPase Pch2 mediates this pattern, likely by means of direct intervention along axes. Pch2 also coordinately promotes timely progression of cross-over (CO) and noncross-over (NCO) recombination. Oppositely, in a checkpoint-triggering aberrant situation (zip1⌬), Pch2 mediates robust arrest of stalled recombination complexes, likely via nucleolar localization. We suggest that, during WT meiosis, Pch2 promotes progression of SC-associated CO and NCO recombination complexes at a regulated early-midpachytene transition that is rate-limiting for later events; in contrast, during defective meiosis, Pch2 ensures that aberrant recombination complexes fail to progress so that intermediates can be harmlessly repaired during eventual return to growth. Positive vs. negative roles of Pch2 in the two situations are analogous to positive vs. negative roles of Mec1/ATR, suggesting that Pch2 might mediate Mec1/ ATR activity. We further propose that regulatory surveillance of normal and abnormal interchromosomal interactions in mitotic and meiotic cells may involve ''structure-dependent interchromosomal interaction'' (SDIX) checkpoints.chromosome architecture ͉ synaptonemal complex ͉ Holliday junction ͉ pachytene ͉ checkpoint

Faithful segregation of homologous chromosomes (homologs) during meiosis depends on chiasmata which correspond to crossovers between parental DNA strands. Crossover forming homologous recombination takes place in the context of the synaptonemal complex (SC), a proteinaceous structure that juxtaposes homologs. The coordination between molecular recombination events and assembly of the SC as a structure that provides global connectivity between homologs represents one of the remarkable features of meiosis. ZMM proteins (also known as the synapsis initiation complex = SIC) play crucial roles in both processes providing a link between recombination and SC assembly. The ZMM group includes at least seven functionally collaborating, yet structurally diverse proteins: The transverse filament protein Zip1 establishes stable homolog juxtaposition by polymerizing as an integral component of the SC. Zip2, Zip3, and Zip4 likely mediate proteinYprotein interactions, while Mer3, Msh4, and Msh5 directly promote steps in DNA recombination. This review focuses on recent insights into ZMM functions in yeast meiosis and draws comparisons to ZMM-related proteins in other model organisms.

Segregation of homologous chromosomes during meiosis I depends on appropriately positioned crossovers/chiasmata. Crossover assurance ensures at least one crossover per homolog pair, while interference reduces double crossovers. Here, we have investigated the interplay between chromosome axis morphogenesis and non-random crossover placement. We demonstrate that chromosome axes are structurally modified at future crossover sites as indicated by correspondence between crossover designation marker Zip3 and domains enriched for axis ensemble Hop1/Red1. This association is first detected at the zygotene stage, persists until double Holliday junction resolution, and is controlled by the conserved AAA+ ATPase Pch2. Pch2 further mediates crossover interference, although it is dispensable for crossover formation at normal levels. Thus, interference appears to be superimposed on underlying mechanisms of crossover formation. When recombination-initiating DSBs are reduced, Pch2 is also required for viable spore formation, consistent with further functions in chiasma formation. pch2Δ mutant defects in crossover interference and spore viability at reduced DSB levels are oppositely modulated by temperature, suggesting contributions of two separable pathways to crossover control. Roles of Pch2 in controlling both chromosome axis morphogenesis and crossover placement suggest linkage between these processes. Pch2 is proposed to reorganize chromosome axes into a tiling array of long-range crossover control modules, resulting in chiasma formation at minimum levels and with maximum spacing.