Meiotic Recombination Pathways

Abstract

Reciprocal recombination between homologous chromosomes in meiosis plays a critical role in promoting accurate reductional chromosome regulation. Meiotic recombination is highly regulated to ensure that at least one reciprocal crossover event occurs between each pair of homologous chromosomes.

Keywords: recombination; meiosis; synaptonemal complex

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 . Orange circles indicate sites of future cleavage by Mus81‐Eme1. Extended D‐loops form as in the ECD model (see Figure ). (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.

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References

Agarwal S and Roeder GS (2000) Zip3 provides a link between recombination enzymes and synaptonemal complex proteins. Cell 102: 245–255.

Allers T and Lichten M (2001) Differential timing and control of noncrossover and crossover recombination during meiosis. Cell 106: 47–57.

Barton NH and Charlesworth B (1998) Why sex and recombination?. Science 281: 1986–1990.

Bishop DK (1994) RecA homologs Dmc1 and Rad51 interact to form multiple nuclear complexes prior to meiotic chromosome synapsis. Cell 79: 1081–1092.

Bishop DK and Zickler D (2004) Early decision; meiotic crossover interference prior to stable strand exchange and synapsis. Cell 117: 9–15.

Börner GV, Kleckner N and Hunter N (2004) Crossover/noncrossover differentiation, synaptonemal complex formation and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 17: 29–45.

Cao L, Alani E and Kleckner N (1990) A pathway for generation and processing of double‐strand breaks during meiotic recombination in S. cerevisiae. Cell 61: 1089–1101.

Carpenter ATC (1988) Thoughts on recombination nodules, meiotic recombination, and chiasmata. In: Smith KA (ed.) Genetic Recombination, pp. 529–548. Washington DC: American Society of Microbiology

Fung JC, Rockmill R, Odell M and Roeder GS (2004) Imposition of crossover interference through the nonrandom distribution of synapsis initiation complexes. Cell 116: 795–802.

Gaillard PH, Noguchi E, Shanahan P and Russell P (2003) The endogenous Mus81‐Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Molecular Cell 12: 747–759.

Hawley RS and Theurkauf WE (1993) Requiem for distributive segregation: achiasmate segregation in Drosophila females. Trends in Genetics 9: 310–317.

Hunter N and Kleckner N (2001) The single‐end invasion: an asymmetric intermediate at the double‐strand break to double‐Holliday junction transition of meiotic recombination. Cell 106: 59–70.

Kadyk LC and Hartwell LH (1992) Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae. Genetics 132: 387–402.

Keeney S (2001) Mechanism and control of meiotic recombination initiation. Current Topics in Developmental Biology 52: 1–53.

Kleckner N, Zickler D, Jones GH et al. (2004) A mechanical basis for chromosome function. Proceedings of the National Academy of Sciences of the USA 101: 12592–12597.

Mazina OM, Mazin AV, Nakagawa T, Kolodner RD and Kowalczykowski SC (2004) The Saccharomyces cerevisiae Mer3 helicase stimulate 3′ to 5′ DNA heteroduplex extension in Rad51‐mediated DNA pairing: implications for cross‐over control in meiotic recombination. Cell 17: 47–56.

Moens PB, Chen DJ, Shen Z et al. (1997) Rad51 immunocytology in rat and mouse spermatocytes and oocytes. Chromosoma 106: 207–215.

Nicklas RB (1997) How cells get the right chromosomes. Science 275: 632–637.

Osman F, Dixon J, Doe CL and Whitby MC (2003) Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81‐Eme1 in meiosis. Molecular Cell 12: 761–774.

Paques F and Haber JE (1999) Multiple pathways of recombination induced by double‐strand breaks in Saccharomyces cerevisiae. Microbiology and Molecular Biology Reviews 63: 349–404.

Petronczki M, Siomos MF and Nasmyth K (2003) Un menage a quatre: the molecular biology of chromosome segregation in meiosis. Cell 112: 423–440.

Roeder GS (1997) Meiotic chromosomes: it takes two to tango. Genes and Development 11: 2600–2621.

Schwacha A and Kleckner N (1995) Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 83: 783–791.

Schwacha A and Kleckner N (1997) Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog‐only pathway. Cell 90: 1123–1135.

Stahl FW (1994) The Holliday junction on its thirtieth anniversary. Genetics 138: 241–246.

Sym M and Roeder GS (1994) Crossover interference is abolished in the absence of a synaptonemal complex protein. Cell 79: 283–292.

Symington LS (2002) Role of RAD52 epistasis group genes in homologous recombination and double‐strand break repair. Microbiology and Molecular Biology Reviews 66: 630–670.

Zickler D and Kleckner N (1999) Meiotic chromosomes: integrating structure and function. Annual Review of Genetics 33: 603–754.

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Bishop, Douglas K(Apr 2006) Meiotic Recombination Pathways. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003875]