Figure 1. Mitotic and meiotic chromosome segregation. (a) Mitotic chromosome segregation. (1a) The chromosome has achieved stable bipolar attachment; sister chromatids are attached to opposite poles at their centromeres. While forces from the poles pull on the centromeres, separation of chromatids is prevented by cohesin that glues the sisters together. (2a) Cohesin is degraded at the metaphase to anaphase transition. (3a) The chromosomes to segregate from one another. (b) A meiotic chromosome is shown at meiotic MI. (1b) The chromosome has achieved stable bipolar attachment; sister centromeres are attached to the same pole, homologous centromeres to opposite poles. Pulling forced from the poles are resisted by chiasmata which are, in turn, prevented from falling apart by the meiotic cohesin located distal to the chiasma with respect to the centromere. (2b) Cohesin is degraded at the MI metaphase/anaphase transition (except in the region proximal to the centromere). (3b) Homologous centromeres disjoin. MII then occurs by a mechanism, similar to that in mitosis. (4b) Centromere proximal cohesin is degraded after bipolar attachment of sister centromeres to the MII spindle and (5b) sisters disjoin.

Figure 2. Structural changes in meiotic chromosomes during recombination. Chromosome structure at different substages of meiotic prophase. Axial elements (red) and recombination nodules (yellow) are first seen in leptotene. Chromatin is relatively uncondensed at this stage. Assembly of transverse filaments (pink) to form the central region of the SC occurs during zygotene as chromatin is condensing. SC assembly is complete in pachytene and chromatin is condensed. Many recombination nodules disappear during late zygotene/early pachytene with remaining nodules marking the sites that will become chiasmata, i.e. the sites of CO events. SCs disappear during diplotene. In addition, chromatin decondenses and then recondenses during this stage. Chiasmata become visible when chromatin recondenses. Inset: Organization of the SC chromatin loops are attached at their base to the lateral elements. Each lateral element organizes a pair of sister chromatids into a ‘parallel’ set of loops. Transverse filaments connect the lateral elements. A recombination nodule sits immediately above the central region of the SC.

Figure 3. The ECD model of recombination. Lines represent ssDNA strands. Green lines indicate newly synthesized DNA. Only the two interacting chromatids are diagrammed (meiotic cells contain two additional chromatids that are not engaged in a given event). (1) A Spo11 dimer, with the aid of multiple accessory factors, forms DSBs via a topoisomerase-like nucleophilic attack remaining covalently attached to 5¢ ends. (2) Spo11 is removed and 5¢ ends are degraded to yield 3¢ overhanging ssDNA tails. (3) RecA-like strand exchange proteins and their accessory factors promote invasion to form D-loops. (a)=Pathway that gives rise to NCOs. (4a) DNA synthesis extends invading 3¢ ends. (5a) The D-loop is disrupted. (6a) ssDNA annealing occurs between the extended end at its partner. (7a) Repair synthesis and ligation complete the formation of the NCO recombinants. (b)=Pathway that gives rise to COs. (4b) The D-loop is enlarged by the action of the Mer3 helicase along with additional factors (e.g. the Zip proteins) to form a stable SEI intermediate. 5b. Synthesis extends the invading 3¢ end and the partner end is captured. (6b) Repair synthesis and ligation results in the formation of a DHJ. 7b. Resolution of the DHJ forms a CO product. Insets: I. Assembly of strand exchange complexes. Secondary structure in ssDNA is removed by binding of single-strand DNA-binding protein (in eukaryotes the SSB is called RPA). Mediator proteins provide a site that allows strand exchange proteins to initiate filament polymerization on RPA-coated DNA. Strand exchange proteins form filaments on ssDNA replacing RPA. II. Mismatch repair. Mismatch in heteroduplex region formed by strand exchange is recognized by repair proteins. A region of ssDNA containing the mismatch is excised by nuclease. Repair synthesis fills in the single-strand gap. III. Key players in the pathway. The names of S. cerevisiae proteins implicated to function at specific stages of recombination are given. More information about the characteristics of these proteins may be found at http://germonline.unibas.ch/ or at http://www.yeastgenome.org/

Figure 4. The D-loop cleavage model for CO formation. Conventions are as in Figure 1. Orange circles indicate sites of future cleavage by Mus81-Eme1. Extended D-loops form as in the ECD model (see Figure 1). (1) D-loops are cleaved. For clarity the resulting branched structure is redrawn with rotation of sequences to the right of the branch. (2) DNA synthesis occurs extending the invading 3¢ end that allows capture of the second end by the displaced ssDNA. (3) A second cleavage event resolves the two chromatids. Repair synthesis and ligation completes formation of a CO product.