Pairing and Synaptonemal Complex Formation Are Independent

KEY CONCEPT
- Mutations can occur in either chromosome pairing or synaptonemal complex formation without affecting the other process.
We can distinguish the processes of pairing and synaptonemal complex formation by the effects of two mutations, each of which blocks one of the processes without affecting the other.
A mutation in the ZMM protein Zip2 allows chromosomes to pair, but they do not form synaptonemal complexes. Thus, recognition between homologs is independent of recombination or synaptonemal complex formation.
The specificity of association between homologous chromosomes is controlled by the gene HOP2 in S. cerevisiae. In hop2 mutants, normal amounts of synaptonemal complex form at meiosis, but the individual complexes contain nonhomologous chromosomes. This suggests that the formation of synaptonemal complexes as such is independent of homology (and therefore cannot be based on any extensive comparison of DNA sequences). The usual role of Hop2 is to prevent nonhomologous chromosomes from interacting.
DSBs form in the mispaired chromosomes in the synaptonemal complexes of hop2 mutants, but they are not repaired. This suggests that, if formation of the synaptonemal complex requires DSBs, it does not require any extensive reaction of these breaks with homologous DNA. It is not clear what usually happens during pachytene, before DNA recombinants are observed. It may be that this period is occupied by the subsequent steps of recombination, which involve the extension of strand exchange, DNA synthesis, and resolution.
At the next stage of meiosis (diplotene), the chromosomes shed the synaptonemal complex; the chiasmata then become visible as points at which the chromosomes are connected. This has been presumed to indicate the occurrence of a genetic exchange, but the molecular nature of a chiasma is unknown. It is possible that it represents the residuum of a completed exchange, or that it represents a connection between homologous chromosomes where a genetic exchange has not yet been resolved. Later in meiosis, the chiasmata move toward the ends of the chromosomes. This flexibility suggests that they represent some remnant of the recombination event rather than providing the actual intermediate.
Recombination events occur at discrete points on meiotic chromosomes, but it is not yet possible to correlate their occurrences with the discrete structures that have been observed; that is, recombination nodules and chiasmata. Insights into the molecular basis for the formation of discontinuous structures, however, are provided by the identification of proteins involved in yeast recombination that can be localized to discrete sites. These include Msh4 (a mismatch repair protein in the ZMM group) and Dmc1 and Rad51 (which are homologs of the Escherichia coli RecA protein). The exact roles of these proteins in recombination remain to be established.
Recombination events are subject to a general control. Only a minority of interactions actually mature as crossovers, but these are distributed in such a way that, in general, each pair of homologs acquires only one to two crossovers, yet the probability of zero crossovers for a homologous pair is very low (less than 0.1%). This process is probably the result of a single crossover control, because the nonrandomness of crossovers is generally disrupted in certain mutants. Furthermore, the occurrence of recombination is necessary for progress through meiosis, and a “checkpoint” system exists to block meiosis if recombination has not occurred. (The block is lifted when recombination has been successfully completed; this system provides a safeguard to ensure that cells do not try to segregate their chromosomes until recombination has occurred.)