genetic crossing over


Summary: The reciprocal exchange of segments at corresponding positions along pairs of homologous CHROMOSOMES by symmetrical breakage and crosswise rejoining forming cross-over sites (HOLLIDAY JUNCTIONS) that are resolved during CHROMOSOME SEGREGATION. Crossing-over typically occurs during MEIOSIS but it may also occur in the absence of meiosis, for example, with bacterial chromosomes, organelle chromosomes, or somatic cell nuclear chromosomes.

Top Publications

  1. Lynn A, Ashley T, Hassold T. Variation in human meiotic recombination. Annu Rev Genomics Hum Genet. 2004;5:317-49 pubmed
  2. McVey M, Andersen S, Broze Y, Sekelsky J. Multiple functions of Drosophila BLM helicase in maintenance of genome stability. Genetics. 2007;176:1979-92 pubmed
    ..We also found that spontaneous mitotic crossovers are increased by several orders of magnitude in mus309 mutants. These results demonstrate that DmBlm functions in multiple cellular contexts to promote genome stability. ..
  3. Stahl F, Foss H, Young L, Borts R, Abdullah M, Copenhaver G. Does crossover interference count in Saccharomyces cerevisiae?. Genetics. 2004;168:35-48 pubmed
    ..The protein-binding pattern required for interference depends on clustering of sites that have received, or are normally about to receive, meiotic double-strand breaks. ..
  4. Mets D, Meyer B. Condensins regulate meiotic DNA break distribution, thus crossover frequency, by controlling chromosome structure. Cell. 2009;139:73-86 pubmed publisher
  5. Buard J, Barthès P, Grey C, de Massy B. Distinct histone modifications define initiation and repair of meiotic recombination in the mouse. EMBO J. 2009;28:2616-24 pubmed publisher
    ..Altogether, the chromatin signatures of the Psmb9 and Hlx1 hotspots provide a basis for understanding the distribution of meiotic recombination. ..
  6. Parvanov E, Ng S, Petkov P, Paigen K. Trans-regulation of mouse meiotic recombination hotspots by Rcr1. PLoS Biol. 2009;7:e36 pubmed publisher
  7. Bhalla N, Wynne D, Jantsch V, Dernburg A. ZHP-3 acts at crossovers to couple meiotic recombination with synaptonemal complex disassembly and bivalent formation in C. elegans. PLoS Genet. 2008;4:e1000235 pubmed publisher
    ..We propose that coordination of crossover recombination with SC disassembly and bivalent formation reflects a conserved role of Zip3/ZHP-3 in coupling recombination with SC morphogenesis. ..
  8. Conrad M, Lee C, Chao G, Shinohara M, Kosaka H, Shinohara A, et al. Rapid telomere movement in meiotic prophase is promoted by NDJ1, MPS3, and CSM4 and is modulated by recombination. Cell. 2008;133:1175-87 pubmed publisher
    ..Together with recombination defects described for ndj1, our observations suggest that RPMs and SCs balance the disruption and stabilization of recombinational interactions, respectively, to regulate crossing over...
  9. Carballo J, Johnson A, Sedgwick S, Cha R. Phosphorylation of the axial element protein Hop1 by Mec1/Tel1 ensures meiotic interhomolog recombination. Cell. 2008;132:758-70 pubmed publisher
    ..Thus, Hop1 is a meiosis-specific adaptor protein of the Mec1/Tel1 signaling pathway that ensures interhomolog recombination by preventing Dmc1-independent repair of meiotic DSBs. ..

More Information


  1. Peters A. A combination of cis and trans control can solve the hotspot conversion paradox. Genetics. 2008;178:1579-93 pubmed publisher
    ..Finally, I show that a combination of cis and trans control may allow for long-lived polymorphisms in hotspot activity, the patterns of which may explain some recently observed features of recombination hotspots. ..
  2. Mezard C. Meiotic recombination hotspots in plants. Biochem Soc Trans. 2006;34:531-4 pubmed
    ..Major efforts should be devoted to characterizing meiotic recombination at the molecular level, which should help to clarify the role of this process in genome evolution. ..
  3. Nelson M, Nixon J, Lydiate D. Genome-wide analysis of the frequency and distribution of crossovers at male and female meiosis in Sinapis alba L. (white mustard). Theor Appl Genet. 2005;111:31-43 pubmed
    ..The possible causes of sex differences in recombination frequency and the implications for plant breeding are discussed...
  4. Nabeshima K, Villeneuve A, Hillers K. Chromosome-wide regulation of meiotic crossover formation in Caenorhabditis elegans requires properly assembled chromosome axes. Genetics. 2004;168:1275-92 pubmed
    ..These results indicate that limiting the amount of a major axis component results in a reduced capacity to communicate the presence of a (nascent) crossover and/or to discourage others in response. ..
  5. Svetlanov A, Baudat F, Cohen P, de Massy B. Distinct functions of MLH3 at recombination hot spots in the mouse. Genetics. 2008;178:1937-45 pubmed publisher
    ..Furthermore, these results indicate that approximately 10% of crossovers in the mouse are independent of MLH3, suggesting the existence of alternative crossover pathways in mammals. ..
  6. Lhuissier F, Offenberg H, Wittich P, Vischer N, Heyting C. The mismatch repair protein MLH1 marks a subset of strongly interfering crossovers in tomato. Plant Cell. 2007;19:862-76 pubmed publisher
    ..Based on the distances between MLH1 foci or LNs, we propose that MLH1-positive and MLH1-negative LNs stem from the same population of weakly interfering precursors...
  7. Baudat F, de Massy B. Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis. Chromosome Res. 2007;15:565-77 pubmed
    ..We discuss the roles of Msh4, Msh5 and Sycp1 which affect DSB repair and probably not only the CO pathway. We suggest that, in mammals, the regulation of NCO differs from that described in Saccharomyces cerevisiae. ..
  8. Lynn A, Soucek R, Börner G. ZMM proteins during meiosis: crossover artists at work. Chromosome Res. 2007;15:591-605 pubmed
    ..This review focuses on recent insights into ZMM functions in yeast meiosis and draws comparisons to ZMM-related proteins in other model organisms. ..
  9. Robert T, Dervins D, Fabre F, Gangloff S. Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover. EMBO J. 2006;25:2837-46 pubmed
    ..Srs2 would prevent formation of double Holliday junctions (dHJs) and thus CO formation. Sgs1 also negatively regulates CO formation but through a different process that resolves dHJs to yield non-CO products. ..
  10. Cromie G, Rubio C, Hyppa R, Smith G. A natural meiotic DNA break site in Schizosaccharomyces pombe is a hotspot of gene conversion, highly associated with crossing over. Genetics. 2005;169:595-605 pubmed
    ..Possible mechanisms for generating crossovers in such break-free intervals are discussed. ..
  11. Perry J, Kleckner N, Börner G. Bioinformatic analyses implicate the collaborating meiotic crossover/chiasma proteins Zip2, Zip3, and Spo22/Zip4 in ubiquitin labeling. Proc Natl Acad Sci U S A. 2005;102:17594-9 pubmed
    ..These and other findings suggest that Zip2, Zip3, and Zip4 act together to mediate a process that involves Zip3-mediated ubiquitin labeling, potentially as a unique type of ubiquitin-conjugating complex. ..
  12. Hassold T, Judis L, Chan E, Schwartz S, Seftel A, Lynn A. Cytological studies of meiotic recombination in human males. Cytogenet Genome Res. 2004;107:249-55 pubmed
    ..We also identified significant among-individual variation in the mean number of exchanges, with an approximate 20% difference between individuals with "low" and those with "high" exchange frequencies. ..
  13. Gong W, McKim K, Hawley R. All paired up with no place to go: pairing, synapsis, and DSB formation in a balancer heterozygote. PLoS Genet. 2005;1:e67 pubmed
  14. Chen S, Tsubouchi T, Rockmill B, Sandler J, Richards D, Vader G, et al. Global analysis of the meiotic crossover landscape. Dev Cell. 2008;15:401-15 pubmed publisher
    ..Lastly, we uncover a surprising role for the synaptonemal complex component Zip1 in repressing crossing over at the centromere...
  15. Wu W, Pujol C, Lockhart S, Soll D. Chromosome loss followed by duplication is the major mechanism of spontaneous mating-type locus homozygosis in Candida albicans. Genetics. 2005;169:1311-27 pubmed
    ..albicans in culture. ..
  16. Jeffreys A, Neumann R, Panayi M, Myers S, Donnelly P. Human recombination hot spots hidden in regions of strong marker association. Nat Genet. 2005;37:601-6 pubmed
    ..These results suggest that hot spots could be very abundant and possibly fluid features of the human genome. ..
  17. Koehler K, Millie E, Cherry J, Schrump S, Hassold T. Meiotic exchange and segregation in female mice heterozygous for paracentric inversions. Genetics. 2004;166:1199-214 pubmed
    ..2%) than in controls (0%), although the frequency was still too low to justify the use of inversion heterozygotes as a model of human nondisjunction. ..
  18. Myers S, Freeman C, Auton A, Donnelly P, McVean G. A common sequence motif associated with recombination hot spots and genome instability in humans. Nat Genet. 2008;40:1124-9 pubmed publisher
  19. Smolikov S, Eizinger A, Hurlburt A, Rogers E, Villeneuve A, COLAIACOVO M. Synapsis-defective mutants reveal a correlation between chromosome conformation and the mode of double-strand break repair during Caenorhabditis elegans meiosis. Genetics. 2007;176:2027-33 pubmed
    ..Moreover, our studies suggest that the conformation of chromosomes may influence the mode of DSB repair employed during meiosis. ..
  20. Joyce E, Tanneti S, McKim K. Drosophila hold'em is required for a subset of meiotic crossovers and interacts with the dna repair endonuclease complex subunits MEI-9 and ERCC1. Genetics. 2009;181:335-40 pubmed publisher
    ..Furthermore, HDM physically interacts with both MEI-9 and ERCC1 in a yeast two-hybrid assay. We conclude that HDM, MEI-9, MUS312, and ERCC1 form a complex that resolves meiotic recombination intermediates into crossovers. ..
  21. Lacefield S, Murray A. The spindle checkpoint rescues the meiotic segregation of chromosomes whose crossovers are far from the centromere. Nat Genet. 2007;39:1273-7 pubmed
    ..The tether partially rescues the segregation of chromosomes that lack crossovers...
  22. Tsai C, Mets D, Albrecht M, Nix P, Chan A, Meyer B. Meiotic crossover number and distribution are regulated by a dosage compensation protein that resembles a condensin subunit. Genes Dev. 2008;22:194-211 pubmed publisher
    ..We propose that both processes utilize a related mechanism involving changes in higher-order chromosome structure to achieve chromosome-wide effects. ..
  23. Coop G, Wen X, Ober C, Pritchard J, Przeworski M. High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans. Science. 2008;319:1395-8 pubmed publisher
    ..Notably, however, we found extensive and heritable variation among both males and females in the proportion of crossovers occurring in these hotspots. ..
  24. Dupaigne P, Le Breton C, Fabre F, Gangloff S, Le Cam E, Veaute X. The Srs2 helicase activity is stimulated by Rad51 filaments on dsDNA: implications for crossover incidence during mitotic recombination. Mol Cell. 2008;29:243-54 pubmed publisher
    ..These properties strongly support the idea that Srs2 actively prevents crossovers by promoting SDSA. ..
  25. Lenzi M, Smith J, Snowden T, Kim M, Fishel R, Poulos B, et al. Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis i in human oocytes. Am J Hum Genet. 2005;76:112-27 pubmed
    ..If such variability persists through development and into adulthood, these data would suggest that as many as 30% of human oocytes are predisposed to aneuploidy as a result of prophase I defects in MutL homolog-related events. ..
  26. Gaskell L, Osman F, Gilbert R, Whitby M. Mus81 cleavage of Holliday junctions: a failsafe for processing meiotic recombination intermediates?. EMBO J. 2007;26:1891-901 pubmed
    ..We also present genetic evidence that suggests that this activity might be utilised as a back-up to Mus81-Eme1's main activity of cleaving nicked HJs during meiosis in S. pombe. ..
  27. Barchi M, Roig I, Di Giacomo M, de Rooij D, Keeney S, Jasin M. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes. PLoS Genet. 2008;4:e1000076 pubmed publisher
    ..Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics. ..
  28. Cromie G, Hyppa R, Smith G. The fission yeast BLM homolog Rqh1 promotes meiotic recombination. Genetics. 2008;179:1157-67 pubmed publisher
    ..These observations underscore the multiple recombination functions of RecQ homologs and emphasize that even conserved proteins can be adapted to play different roles in different organisms. ..
  29. Greenawalt D, Cui X, Wu Y, Lin Y, Wang H, Luo M, et al. Strong correlation between meiotic crossovers and haplotype structure in a 2.5-Mb region on the long arm of chromosome 21. Genome Res. 2006;16:208-14 pubmed
    ..This finding supports the hypothesis that meiotic recombination makes a primary contribution to haplotype block formation in the human genome. ..
  30. Peoples Holst T, Burgess S. Multiple branches of the meiotic recombination pathway contribute independently to homolog pairing and stable juxtaposition during meiosis in budding yeast. Genes Dev. 2005;19:863-74 pubmed
    ..We suggest that transient, early DSB-initiated interactions, including those that give rise to noncrossovers, are important for homolog recognition and juxtaposition. ..
  31. Esch E. Estimation of gametic frequencies from F2 populations using the EM algorithm and its application in the analysis of crossover interference in rice. Theor Appl Genet. 2005;111:100-9 pubmed
    ..The strength of the centromere effect on interference seemed to depend on the strength of recombination suppression around the centromere. ..
  32. Lam S, Horn S, Radford S, Housworth E, Stahl F, Copenhaver G. Crossover interference on nucleolus organizing region-bearing chromosomes in Arabidopsis. Genetics. 2005;170:807-12 pubmed
    ..Since these two chromosomes bear the Arabidopsis NOR domains, the possibility that these chromosomal regions influence interference is discussed. ..
  33. Sun F, Oliver Bonet M, Liehr T, Starke H, Turek P, Ko E, et al. Analysis of non-crossover bivalents in pachytene cells from 10 normal men. Hum Reprod. 2006;21:2335-9 pubmed
  34. Rockmill B, Voelkel Meiman K, Roeder G. Centromere-proximal crossovers are associated with precocious separation of sister chromatids during meiosis in Saccharomyces cerevisiae. Genetics. 2006;174:1745-54 pubmed
    ..We present a model for PSSC in which a centromere-proximal CO promotes local loss of sister-chromatid cohesion. ..
  35. Jones G, Franklin F. Meiotic crossing-over: obligation and interference. Cell. 2006;126:246-8 pubmed
    ..In this issue of Cell, Martini et al., (2006) report that the reduction of crossover-initiating events does not result in fewer crossovers. These results have important implications for our understanding of crossover control. ..
  36. Radford S, McMahan S, Blanton H, Sekelsky J. Heteroduplex DNA in meiotic recombination in Drosophila mei-9 mutants. Genetics. 2007;176:63-72 pubmed
  37. Malkova A, Swanson J, German M, McCusker J, Housworth E, Stahl F, et al. Gene conversion and crossing over along the 405-kb left arm of Saccharomyces cerevisiae chromosome VII. Genetics. 2004;168:49-63 pubmed
  38. Bhagat R, Manheim E, Sherizen D, McKim K. Studies on crossover-specific mutants and the distribution of crossing over in Drosophila females. Cytogenet Genome Res. 2004;107:160-71 pubmed
    ..This may be the activation of a regulatory system that ensures at least one crossover per chromosome, and which compensates for an absence of crossovers by attempting to generate them at random locations. ..
  39. de Boer E, Dietrich A, Hoog C, Stam P, Heyting C. Meiotic interference among MLH1 foci requires neither an intact axial element structure nor full synapsis. J Cell Sci. 2007;120:731-6 pubmed
    ..The levels of interference among MLH1 foci in wild-type and Sycp3(-/-) mice were comparable, implying that neither an intact AE structure nor full synapsis is required for wild-type levels of interference. ..
  40. Kauppi L, Stumpf M, Jeffreys A. Localized breakdown in linkage disequilibrium does not always predict sperm crossover hot spots in the human MHC class II region. Genomics. 2005;86:13-24 pubmed
    ..These results highlight the complexity of LD patterns and the importance of experimentally verifying crossover hot spots...
  41. Abdullah M, Hoffmann E, Cotton V, Borts R. A role for the MutL homologue MLH2 in controlling heteroduplex formation and in regulating between two different crossover pathways in budding yeast. Cytogenet Genome Res. 2004;107:180-90 pubmed
    ..The minor pathway(s) utilizes Mms4p/Mus81p. We suggest that the absence of Mlh2p allows some crossovers from the MSH4 pathway to traverse the MUS81-dependent pathway. ..
  42. Lim J, Stine R, Yanowitz J. Domain-specific regulation of recombination in Caenorhabditis elegans in response to temperature, age and sex. Genetics. 2008;180:715-26 pubmed publisher
    ..Our data enhance the emerging hypothesis that recombination in C. elegans, as in humans, is regulated in large chromosomal domains. ..
  43. de Vries F, de Boer E, van den Bosch M, Baarends W, Ooms M, Yuan L, et al. Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation. Genes Dev. 2005;19:1376-89 pubmed
    ..Crossovers were rare in metaphase I of Sycp1(-/-) mice. We propose that SYCP1 has a coordinating role, and ensures formation of crossovers. Unexpectedly, Sycp1(-/-) spermatocytes did not form XY bodies...
  44. Ng S, Parvanov E, Petkov P, Paigen K. A quantitative assay for crossover and noncrossover molecular events at individual recombination hotspots in both male and female gametes. Genomics. 2008;92:204-9 pubmed publisher
    ..Using this technique, we analyzed recombination events at the Hlx1 hotspot located on mouse chromosome 1, finding that the results agree well with a prior genetic characterization of 3026 male and 3002 female meioses...
  45. MacQueen A, Phillips C, Bhalla N, Weiser P, Villeneuve A, Dernburg A. Chromosome sites play dual roles to establish homologous synapsis during meiosis in C. elegans. Cell. 2005;123:1037-50 pubmed
    ..We speculate that concentration of these activities at one region per chromosome may have coevolved with the loss of a point centromere to safeguard karyotype stability. ..
  46. Oh S, Lao J, Hwang P, Taylor A, Smith G, Hunter N. BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell. 2007;130:259-72 pubmed
    ..Thus, by disrupting aberrant JMs, BLM-related helicases maximize repair efficiency while minimizing the risk of deleterious crossing-over. ..
  47. Jolivet S, Vezon D, Froger N, Mercier R. Non conservation of the meiotic function of the Ski8/Rec103 homolog in Arabidopsis. Genes Cells. 2006;11:615-22 pubmed
    ..The data presented here provide strong evidence that the meiotic role of Ski8 is not conserved in Arabidopsis and sequence analysis suggests that this may also be the case in a range of other species. ..
  48. Coop G, Przeworski M. An evolutionary view of human recombination. Nat Rev Genet. 2007;8:23-34 pubmed
  49. Sun F, Oliver Bonet M, Liehr T, Starke H, Turek P, Ko E, et al. Variation in MLH1 distribution in recombination maps for individual chromosomes from human males. Hum Mol Genet. 2006;15:2376-91 pubmed
    ..Inter-individual variation in interference distances was observed for all chromosomes. The significance of altered recombination patterns among individuals and the role of interference are discussed. ..
  50. Yoo S, McKee B. Functional analysis of the Drosophila Rad51 gene (spn-A) in repair of DNA damage and meiotic chromosome segregation. DNA Repair (Amst). 2005;4:231-42 pubmed
    ..Our results also provide the first demonstration that RNAi can be used to inhibit the functions of meiotic genes in Drosophila. ..
  51. Bugreev D, Mazina O, Mazin A. Rad54 protein promotes branch migration of Holliday junctions. Nature. 2006;442:590-3 pubmed
    ..13). Novel DNA branch-migration activity is fully consistent with this late homologous recombination function of Rad54 protein. ..
  52. Radford S, Goley E, Baxter K, McMahan S, Sekelsky J. Drosophila ERCC1 is required for a subset of MEI-9-dependent meiotic crossovers. Genetics. 2005;170:1737-45 pubmed
    ..We conclude that MEI-9 can generate some meiotic crossovers in an ERCC1-independent manner. ..
  53. Drouaud J, Camilleri C, Bourguignon P, Canaguier A, Bérard A, Vezon D, et al. Variation in crossing-over rates across chromosome 4 of Arabidopsis thaliana reveals the presence of meiotic recombination "hot spots". Genome Res. 2006;16:106-14 pubmed
    ..Both the intensity and the density of these hot spots explain the variation of CO rates along the chromosome. ..