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  • Review Article
  • Published:

Finding a match: how do homologous sequences get together for recombination?

Nature Reviews Genetics volume 9, pages 27–37 (2008)Cite this article

Key Points

  • Homologous recombination (HR) is a universal DNA repair mechanism that faithfully restores genomic integrity following double-strand breaks (DSBs) in DNA.

  • The details concerning the transfer of information between two interacting homologous sequences have been uncovered. However, little is known about the processes by which the molecules colocalize.

  • HR takes place efficiently even between homologous sequences located on different chromosomes. Following the creation of a single DSB in a yeast chromosome, a genome-wide search for homology can allow repair by HR in 100% of the cells in less than 2 hours.

  • A basic model of homology search in which the broken arms randomly search throughout the whole genome for homologous sequences cannot account for the efficiency and the speed at which repair occurs and presents spatial and topological problems.

  • An alternative possibility is that homologous sequences are already paired before the DSB. However, evidence for such somatic pairing is controversial in many species.

  • In many organisms, centromeres tend to aggregate in vegetative cells (the Rabl configuration) and telomeres merge in meiotic cells (the 'bouquet' configuration). Such spatial genome organization brings allelic loci closer together and might aid homologous pairing.

  • During meiosis, homologous chromosomes pair and engage in HR. In some organisms, such as yeast, plants and animals, pairing depends on DSB formation. By contrast, pairing in worms and flies is independent of DSB formation.

  • In mammalian cells, chromosomes are organized in discrete non-overlapping chromosome territories; here, non-homologous end joining is the preponderant DSB repair mechanism. However, the compartmentalization of the genome is not stringent and HR occurs at significant rates.

  • In several species, homologous pairing has important functions in genetic and epigenetic processes other than DNA repair.

Abstract

Decades of research into homologous recombination have unravelled many of the details concerning the transfer of information between two homologous sequences. By contrast, the processes by which the interacting molecules initially colocalize are largely unknown. How can two homologous needles find each other in the genomic haystack? Is homologous pairing the result of a damage-induced homology search, or is it an enduring and general feature of the genomic architecture that facilitates homologous recombination whenever and wherever damage occurs? This Review presents the homologous-pairing enigma, delineates our current understanding of the process and offers guidelines for future research.

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Figure 1: Ectopic recombination assay induced by a double-strand break (DSB).
Figure 2: Homologous pairing: damage-induced or constitutive?
Figure 3: Assays for somatic pairing.
Figure 4: Rabl and bouquet conformations.

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References

  1. Aylon, Y. & Kupiec, M. DSB repair: the yeast paradigm. DNA Repair (Amst.) 3, 797–815 (2004).

    Article  CAS  Google Scholar 

  2. Gerton, J. L. & Hawley, R. S. Homologous chromosome interactions in meiosis: diversity amidst conservation. Nature Rev. Genet. 6, 477–487 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Haber, J. E., Ira, G., Malkova, A. & Sugawara, N. Repairing a double-strand chromosome break by homologous recombination: revisiting Robin Holliday's model. Philos. Trans. R. Soc. Lond. B Biol. Sci. 359, 79–86 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Stoddard, B. L. Homing endonuclease structure and function. Q. Rev. Biophys. 38, 49–95 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Thomas, C. M. & Nielsen, K. M. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nature Rev. Microbiol. 3, 711–721 (2005).

    Article  CAS  Google Scholar 

  6. Holliday, R. A mechanism for gene conversion in fungi. Genet. Res. 5, 282–290 (1964).

    Article  Google Scholar 

  7. Meselson, M. S. & Radding, C. M. A general model for genetic recombination. Proc. Natl Acad. Sci. USA 72, 358–361 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nassif, N., Penney, J., Pal, S., Engels, W. R. & Gloor, G. B. Efficient copying of nonhomologous sequences from ectopic sites via P-element-induced gap repair. Mol. Cell. Biol. 14, 1613–1625 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Szostak, J. W., Orr-Weaver, T. L., Rothstein, R. J. & Stahl, F. W. The double-strand-break repair model for recombination. Cell 33, 25–35 (1983). The models presented in references 8 and 9 (with slight modifications) constitute the current view of the molecular mechanisms of DSB repair.

    Article  CAS  PubMed  Google Scholar 

  10. Schubert, V. et al. Random homologous pairing and incomplete sister chromatid alignment are common in angiosperm interphase nuclei. Mol. Genet. Genomics 278, 167–176 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Kadyk, L. C. & Hartwell, L. H. Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae. Genetics 132, 387–402 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Aylon, Y., Liefshitz, B., Bitan-Banin, G. & Kupiec, M. Molecular dissection of mitotic recombination in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol. 23, 1403–1417 (2003). A dissection of the mechanism of repair of a single, defined DSB by ectopic HR. This study exemplifies the high efficiency by which a small region of homology is searched for, detected and used to repair a single DSB.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Storici, F., Bebenek, K., Kunkel, T. A., Gordenin, D. A. & Resnick, M. A. RNA-templated DNA repair. Nature 447, 338–341 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Aylon, Y. & Kupiec, M. The checkpoint protein Rad24 of Saccharomyces cerevisiae is involved in processing double-strand break ends and in recombination partner choice. Mol. Cell. Biol. 23, 6585–6596 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fairhead, C. & Dujon, B. Consequences of unique double-stranded breaks in yeast chromosomes: death or homozygosis. Mol. Gen. Genet. 240, 170–178 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Krogh, B. O. & Symington, L. S. Recombination proteins in yeast. Annu. Rev. Genet. 38, 233–271 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Bell, C. E. Structure and mechanism of Escherichia coli RecA ATPase. Mol. Microbiol. 58, 358–366 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Sagi, D., Tlusty, T. & Stavans, J. High fidelity of RecA-catalyzed recombination: a watchdog of genetic diversity. Nucleic Acids Res. 34, 5021–5031 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rao, B. J., Chiu, S. K., Bazemore, L. R., Reddy, G. & Radding, C. M. How specific is the first recognition step of homologous recombination? Trends Biochem. Sci. 20, 109–113 (1995).

    Article  CAS  PubMed  Google Scholar 

  20. Kupiec, M. & Petes, T. D. Allelic and ectopic recombination between Ty elements in yeast. Genetics 119, 549–559 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ira, G. et al. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 431, 1011–1017 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Inbar, O. & Kupiec, M. Homology search and choice of homologous partner during mitotic recombination. Mol. Cell. Biol. 19, 4134–4142 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Parket, A., Inbar, O. & Kupiec, M. Recombination of Ty elements in yeast can be induced by a double-strand break. Genetics 140, 67–77 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Inbar, O., Liefshitz, B., Bitan, G. & Kupiec, M. The relationship between homology length and crossing over during the repair of a broken chromosome. J. Biol. Chem. 275, 30833–30838 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Inbar, O. & Kupiec, M. Recombination between divergent sequences leads to cell death in a mismatch-repair-independent manner. Curr. Genet. 38, 23–32 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. Sweetser, D. B., Hough, H., Whelden, J. F., Arbuckle, M. & Nickoloff, J. A. Fine-resolution mapping of spontaneous and double-strand break-induced gene conversion tracts in Saccharomyces cerevisiae reveals reversible mitotic conversion polarity. Mol. Cell. Biol. 14, 3863–3875 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Aylon, Y., Liefshitz, B. & Kupiec, M. The CDK regulates repair of double-strand breaks by homologous recombination during the cell cycle. Embo J. 23, 4868–4875 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lisby, M. & Rothstein, R. DNA repair: keeping it together. Curr. Biol. 14, R994–R996 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Ronshaugen, M. & Levine, M. Visualization of trans-homolog enhancer–promoter interactions at the Abd-B Hox locus in the Drosophila embryo. Dev. Cell 7, 925–932 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Goldman, A. S. & Lichten, M. The efficiency of meiotic recombination between dispersed sequences in Saccharomyces cerevisiae depends upon their chromosomal location. Genetics 144, 43–55 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Lichten, M. & Haber, J. E. Position effects in ectopic and allelic mitotic recombination in Saccharomyces cerevisiae. Genetics 123, 261–268 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Jinks-Robertson, S. & Petes, T. D. Chromosomal translocations generated by high-frequency meiotic recombination between repeated yeast genes. Genetics 114, 731–752 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Schlecht, H. B., Lichten, M. & Goldman, A. S. Compartmentalization of the yeast meiotic nucleus revealed by analysis of ectopic recombination. Genetics 168, 1189–1203 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Goldman, A. S. & Lichten, M. Restriction of ectopic recombination by interhomolog interactions during Saccharomyces cerevisiae meiosis. Proc. Natl Acad. Sci. USA 97, 9537–9542 (2000). This paper shows that decreasing recombination between homologues in yeast meiosis elevates the frequency of ectopic recombination, indicating that allelic pairing might restrict the ability of ectopically located sequences to find each other and recombine.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Paques, F. & Haber, J. E. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 63, 349–404 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Weiner, B. M. & Kleckner, N. Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell 77, 977–991 (1994). This study pioneered the use of fluorescent chromosomal markers to map interactions between homologues.

    Article  CAS  PubMed  Google Scholar 

  37. Burgess, S. M., Kleckner, N. & Weiner, B. M. Somatic pairing of homologs in budding yeast: existence and modulation. Genes Dev. 13, 1627–1641 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Burgess, S. M. & Kleckner, N. Collisions between yeast chromosomal loci in vivo are governed by three layers of organization. Genes Dev. 13, 1871–1883 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Dekker, J., Rippe, K., Dekker, M. & Kleckner, N. Capturing chromosome conformation. Science 295, 1306–1311 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Jin, Q. W., Fuchs, J. & Loidl, J. Centromere clustering is a major determinant of yeast interphase nuclear organization. J. Cell Sci. 113, 1903–1912 (2000).

    CAS  PubMed  Google Scholar 

  41. Lorenz, A., Fuchs, J., Burger, R. & Loidl, J. Chromosome pairing does not contribute to nuclear architecture in vegetative yeast cells. Eukaryotic Cell 2, 856–866 (2003). This study re-analyses the results observed by the Kleckner laboratory and concludes that there is no evidence for somatic (pre-meiotic) pairing.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Aragon-Alcaide, L. & Strunnikov, A. V. Functional dissection of in vivo interchromosome association in Saccharomyces cerevisiae. Nature Cell Biol. 2, 812–818 (2000). Using fluorescent chromosomal tags, these authors detect the association of tagged chromosomal domains irrespective of their genomic location, with some preference for similar chromosomal positions.

    Article  CAS  PubMed  Google Scholar 

  43. Lisby, M. & Rothstein, R. DNA damage checkpoint and repair centers. Curr. Opin. Cell Biol. 16, 328–334 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Rong, Y. S. & Golic, K. G. The homologous chromosome is an effective template for the repair of mitotic DNA double-strand breaks in Drosophila. Genetics 165, 1831–1842 (2003). This paper describes high rates of homologous pairing and recombination in D. melanogaster.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Gemkow, M. J., Verveer, P. J. & Arndt-Jovin, D. J. Homologous association of the Bithorax-Complex during embryogenesis: consequences for transvection in Drosophila melanogaster. Development 125, 4541–4552 (1998).

    CAS  PubMed  Google Scholar 

  46. Prieto, P., Santos, A. P., Moore, G. & Shaw, P. Chromosomes associate premeiotically and in xylem vessel cells via their telomeres and centromeres in diploid rice (Oryza sativa). Chromosoma 112, 300–307 (2004).

    Article  PubMed  Google Scholar 

  47. Scherthan, H., Bahler, J. & Kohli, J. Dynamics of chromosome organization and pairing during meiotic prophase in fission yeast. J. Cell Biol. 127, 273–285 (1994).

    Article  CAS  PubMed  Google Scholar 

  48. Xu, N., Tsai, C. L. & Lee, J. T. Transient homologous chromosome pairing marks the onset of X inactivation. Science 311, 1149–1152 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Hogart, A., Nagarajan, R. P., Patzel, K. A., Yasui, D. H. & Lasalle, J. M. 15q11–13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum. Mol. Genet. 16, 691–703 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Fraser, P. & Bickmore, W. Nuclear organization of the genome and the potential for gene regulation. Nature 447, 413–417 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Spector, D. L. The dynamics of chromosome organization and gene regulation. Annu. Rev. Biochem. 72, 573–608 (2003).

    Article  CAS  PubMed  Google Scholar 

  52. Mahy, N. L., Perry, P. E., Gilchrist, S., Baldock, R. A. & Bickmore, W. A. Spatial organization of active and inactive genes and noncoding DNA within chromosome territories. J. Cell Biol. 157, 579–589 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Dehghani, H., Dellaire, G. & Bazett-Jones, D. P. Organization of chromatin in the interphase mammalian cell. Micron 36, 95–108 (2005).

    Article  PubMed  Google Scholar 

  54. Lanctot, C., Cheutin, T., Cremer, M., Cavalli, G. & Cremer, T. Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nature Rev. Genet. 8, 104–115 (2007). This Review describes the current view of the dynamic functional organization of the nucleus, in which genomic regions undergo repositioning relative to each other and to nuclear subcompartments.

    Article  CAS  PubMed  Google Scholar 

  55. Brown, J. M. et al. Coregulated human globin genes are frequently in spatial proximity when active. J. Cell Biol. 172, 177–187 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sullivan, G. J. et al. Human acrocentric chromosomes with transcriptionally silent nucleolar organizer regions associate with nucleoli. Embo J. 20, 2867–2874 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lee, G. R., Spilianakis, C. G. & Flavell, R. A. Hypersensitive site 7 of the TH2 locus control region is essential for expressing TH2 cytokine genes and for long-range intrachromosomal interactions. Nature Immunol. 6, 42–48 (2005).

    Article  CAS  Google Scholar 

  58. Lomvardas, S. et al. Interchromosomal interactions and olfactory receptor choice. Cell 126, 403–413 (2006).

    Article  CAS  PubMed  Google Scholar 

  59. Abdel-Halim, H. I., Mullenders, L. H. & Boei, J. J. Pairing of heterochromatin in response to cellular stress. Exp. Cell Res. 312, 1961–1969 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Soutoglou, E. et al. Positional stability of single double-strand breaks in mammalian cells. Nature Cell Biol. 9, 675–682 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Burma, S., Chen, B. P. & Chen, D. J. Role of non-homologous end joining (NHEJ) in maintaining genomic integrity. DNA Repair (Amst.) 5, 1042–1048 (2006).

    Article  CAS  Google Scholar 

  62. Lim, D. S. & Hasty, P. A mutation in mouse Rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Mol. Cell. Biol. 16, 7133–7143 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Baker, M. D., Read, L. R., Ng, P. & Beatty, B. G. Intrachromosomal recombination between well-separated, homologous sequences in mammalian cells. Genetics 152, 685–697 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Schildkraut, E., Miller, C. A. & Nickoloff, J. A. Gene conversion and deletion frequencies during double-strand break repair in human cells are controlled by the distance between direct repeats. Nucleic Acids Res. 33, 1574–1580 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tremblay, A., Jasin, M. & Chartrand, P. A double-strand break in a chromosomal LINE element can be repaired by gene conversion with various endogenous LINE elements in mouse cells. Mol. Cell. Biol. 20, 54–60 (2000). This paper presents evidence for ectopic recombination in mammalian cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Shinohara, A. & Shinohara, M. Roles of RecA homologues Rad51 and Dmc1 during meiotic recombination. Cytogenet. Genome Res. 107, 201–207 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Padmore, R., Cao, L. & Kleckner, N. Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. Cell 66, 1239–1256 (1991). A landmark paper demonstrating that, in yeast meiosis, DSBs appear before the synaptonemal complex and pairing.

    Article  CAS  PubMed  Google Scholar 

  68. Tsubouchi, T. & Roeder, G. S. A synaptonemal complex protein promotes homology-independent centromere coupling. Science 308, 870–873 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. Phillips, C. M. et al. HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis. Cell 123, 1051–1063 (2005). This landmark paper describes a protein that recognizes a chromosome-specific pairing centre during C. elegans meiosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. MacQueen, A. J. et al. Chromosome sites play dual roles to establish homologous synapsis during meiosis in C. elegans. Cell 123, 1037–1050 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Thomas, S. E. et al. Identification of two proteins required for conjunction and regular segregation of achiasmate homologs in Drosophila male meiosis. Cell 123, 555–568 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Cheslock, P. S., Kemp, B. J., Boumil, R. M. & Dawson, D. S. The roles of MAD1, MAD2 and MAD3 in meiotic progression and the segregation of nonexchange chromosomes. Nature Genet. 37, 756–760 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Dernburg, A. F., Sedat, J. W. & Hawley, R. S. Direct evidence of a role for heterochromatin in meiotic chromosome segregation. Cell 86, 135–146 (1996).

    Article  CAS  PubMed  Google Scholar 

  74. Scherthan, H. Telomere attachment and clustering during meiosis. Cell. Mol. Life Sci. 64, 117–124 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Trelles-Sticken, E., Dresser, M. E. & Scherthan, H. Meiotic telomere protein Ndj1p is required for meiosis-specific telomere distribution, bouquet formation and efficient homologue pairing. J. Cell Biol. 151, 95–106 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Wu, H. Y. & Burgess, S. M. Ndj1, a telomere-associated protein, promotes meiotic recombination in budding yeast. Mol. Cell. Biol. 26, 3683–3694 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cooper, J. P., Watanabe, Y. & Nurse, P. Fission yeast Taz1 protein is required for meiotic telomere clustering and recombination. Nature 392, 828–831 (1998).

    Article  CAS  PubMed  Google Scholar 

  78. Liu, L. et al. Irregular telomeres impair meiotic synapsis and recombination in mice. Proc. Natl Acad. Sci. USA 101, 6496–6501 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chikashige, Y. et al. Meiotic proteins bqt1 and bqt2 tether telomeres to form the bouquet arrangement of chromosomes. Cell 125, 59–69 (2006).

    Article  CAS  PubMed  Google Scholar 

  80. Zickler, D. Development of the synaptonemal complex and the 'recombination nodules' during meiotic prophase in the seven bivalents of the fungus Sordaria macrospora Auersw. Chromosoma 61, 289–316 (1977).

    Article  CAS  PubMed  Google Scholar 

  81. Noguchi, J. Homolog pairing and two kinds of bouquets in the meiotic prophase of rye, Secale cereale. Genes Genet. Syst. 77, 39–50 (2002).

    Article  PubMed  Google Scholar 

  82. Keeney, S. & Neale, M. J. Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation. Biochem. Soc. Trans. 34, 523–525 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Wilson, P. J., Riggs, C. D. & Hasenkampf, C. A. Plant chromosome homology: hypotheses relating rendezvous, recognition and reciprocal exchange. Cytogenet. Genome Res. 109, 190–197 (2005).

    Article  CAS  PubMed  Google Scholar 

  84. McKee, B. D. Pairing sites and the role of chromosome pairing in meiosis and spermatogenesis in male Drosophila. Curr. Top. Dev. Biol. 37, 77–115 (1998).

    Article  CAS  PubMed  Google Scholar 

  85. Pecinka, A. et al. Chromosome territory arrangement and homologous pairing in nuclei of Arabidopsis thaliana are predominantly random except for NOR-bearing chromosomes. Chromosoma 113, 258–269 (2004).

    Article  CAS  PubMed  Google Scholar 

  86. Zirbel, R. M., Mathieu, U. R., Kurz, A., Cremer, T. & Lichter, P. Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries. Chromosome Res. 1, 93–106 (1993).

    Article  CAS  PubMed  Google Scholar 

  87. Melamed, C., Nevo, Y. & Kupiec, M. Involvement of cDNA in homologous recombination between Ty elements in Saccharomyces cerevisiae. Mol. Cell. Biol. 12, 1613–1620 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Torres-Rosell, J. et al. The Smc5–Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nature Cell Biol. 9, 923–931 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Shinohara, A., Gasior, S., Ogawa, T., Kleckner, N. & Bishop, D. K. Saccharomyces cerevisiae RecA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination. Genes Cells 2, 615–629 (1997).

    Article  CAS  PubMed  Google Scholar 

  90. Duncan, I. W. Transvection effects in Drosophila. Annu. Rev. Genet. 36, 521–556 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Lewis, E. B. Regulation of the genes of the bithorax complex in Drosophila. Cold Spring Harb. Symp. Quant. Biol. 50, 155–164 (1985).

    Article  CAS  PubMed  Google Scholar 

  92. Galagan, J. E. & Selker, E. U. RIP: the evolutionary cost of genome defense. Trends Genet. 20, 417–423 (2004).

    Article  CAS  PubMed  Google Scholar 

  93. Rossignol, J. L. & Faugeron, G. Gene inactivation triggered by recognition between DNA repeats. Experientia 50, 307–317 (1994).

    Article  CAS  PubMed  Google Scholar 

  94. Henderson, I. R. & Jacobsen, S. E. Epigenetic inheritance in plants. Nature 447, 418–424 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Chicas, A., Cogoni, C. & Macino, G. RNAi-dependent and RNAi-independent mechanisms contribute to the silencing of RIPed sequences in Neurospora crassa. Nucleic Acids Res. 32, 4237–4243 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Skarn, M. et al. An inverted repeat transgene with a structure that cannot generate double-stranded RNA, suffers silencing independent of DNA methylation. Transgenic Res. 15, 489–500 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Chi, P., San Filippo, J., Sehorn, M. G., Petukhova, G. V. & Sung, P. Bipartite stimulatory action of the Hop2–Mnd1 complex on the Rad51 recombinase. Genes Dev. 21, 1747–1757 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Ploquin, M. et al. Stimulation of fission yeast and mouse Hop2–Mnd1 of the Dmc1 and Rad51 recombinases. Nucleic Acids Res. 35, 2719–2733 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Deng, Z. Y. & Wang, T. OsDMC1 is required for homologous pairing in Oryza sativa. Plant Mol. Biol. 65, 31–42 (2007).

    Article  CAS  PubMed  Google Scholar 

  100. Schwacha, A. & Kleckner, N. Identification of joint molecules that form frequently between homologs but rarely between sister chromatids during yeast meiosis. Cell 76, 51–63 (1994).

    Article  CAS  PubMed  Google Scholar 

  101. Niu, H. et al. Mek1 kinase is regulated to suppress double-strand break repair between sister chromatids during budding yeast meiosis. Mol. Cell. Biol. 27, 5456–5467 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wan, L., de los Santos, T., Zhang, C., Shokat, K. & Hollingsworth, N. M. Mek1 kinase activity functions downstream of RED1 in the regulation of meiotic double strand break repair in budding yeast. Mol. Biol. Cell 15, 11–23 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Work on the mechanism of homology search during DSB repair was supported by grants to M.K. from the Israel Science Foundation. We apologize to authors whose work we could not cite owing to space constraints. We would like to thank all members of the Kupiec laboratory for help and encouragement. We are grateful to J. Loidl and A. Strunnikov for providing the images used in Fig. 3.

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  1. Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, 69978, Israel

    Adi Barzel & Martin Kupiec

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  1. Adi Barzel
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Glossary

Homing endonucleases

A large and universal class of nucleases, usually encoded by mobile genetic elements such as group I introns and inteins, that promote their own dissemination by homologous recombination.

Integrative transformation

A process by which a linear molecule of DNA is introduced into a cell and is incorporated into its genome.

High-frequency recombination conjugation

A mechanism by which bacteria can exchange large chromosomal fragments.

General transduction

A process in which bacterial viruses transfer chromosomal regions between bacteria.

Heteroduplex DNA

A DNA molecule generated by annealing of complementary single strands derived from different parental duplex molecules. Heteroduplex DNA often contains mismatches.

Isogenic strains

Strains that are genetically identical, except for a single, or a few, specific trait(s).

Transvection

A trans effect on gene expression that is conveyed between homologous regulatory regions, such as enhancers or silencers.

Nucleolar organizing region

A chromosomal segment, rich in ribosomal DNA (rDNA), that has the ability to organize the nucleolus around it.

X inactivation

The process in which one X chromosome in each cell of the female embryo is inactivated.

Cis-acting pairing centres

Chromosomal regions that are important for pairing of homologues during meiosis.

Distributive disjunction

The meiotic segregation of chromosomes that did not engage in recombination.

Transcription factory

A nuclear subcompartment that is rich in RNA polymerases and transcription factors where dispersed genes gather to become active.

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Barzel, A., Kupiec, M. Finding a match: how do homologous sequences get together for recombination?. Nat Rev Genet 9, 27–37 (2008). https://doi.org/10.1038/nrg2224

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