Mechanisms and principles of homology search during recombination

Key Points

  • Homology search is the crucial step during homologous recombination that involves the encounter of two homologous sequences, the constant probing for homology and the final recognition of the homologous site.

  • The mechanism of homology search, which was previously considered to be one of the most enigmatic processes in DNA double-strand break (DSB) repair, is now partially understood owing to several methodological advances.

  • The proposed 'accelerated random search model' suggests that homology search functions by a random probing mechanism that is carried out by the RecA or RAD51 presynaptic nucleoprotein filament in three dimensions. However, the model further suggests that probing is accelerated by engaging multiple contacts of the filament with DNA and by sliding of the filament along DNA.

  • As spatial proximity seems to be a key determinant of efficient homology search, chromatin architecture and nuclear organization have a decisive role during the search process.

  • Mediators of homology search are either proteins or structures that restrict and guide the search to donor sequences, or factors that actively facilitate homology probing in the context of chromatin and histones.

Abstract

Homologous recombination is crucial for genome stability and for genetic exchange. Although our knowledge of the principle steps in recombination and its machinery is well advanced, homology search, the critical step of exploring the genome for homologous sequences to enable recombination, has remained mostly enigmatic. However, recent methodological advances have provided considerable new insights into this fundamental step in recombination that can be integrated into a mechanistic model. These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process. They also aid our understanding of how homology search might lead to unwanted and potentially disease-promoting recombination events.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Homology probing in vitro.
Figure 2: Accelerated random search model.

References

  1. 1

    Heyer, W. D., Ehmsen, K. T. & Liu, J. Regulation of homologous recombination in eukaryotes. Annu. Rev. Genet. 44, 113–139 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2

    de Massy, B. Initiation of meiotic recombination: how and where? Conservation and specificities among eukaryotes. Annu. Rev. Genet. 47, 563–599 (2013).

    CAS  Article  PubMed  Google Scholar 

  3. 3

    Haber, J. E. Mating-type genes and MAT switching in Saccharomyces cerevisiae. Genetics 191, 33–64 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Holliday, R. A mechanism for gene conversion in fungi. Genet. Res. 5, 282–304 (1964).

    Article  Google Scholar 

  5. 5

    Weiner, A., Zauberman, N. & Minsky, A. Recombinational DNA repair in a cellular context: a search for the homology search. Nature Rev. Microbiol. 7, 748–755 (2009). This important review argues against a genome-wide homology search, mainly on the basis of theoretical considerations.

    CAS  Article  Google Scholar 

  6. 6

    Barzel, A. & Kupiec, M. Finding a match: how do homologous sequences get together for recombination? Nature Rev. Genet. 9, 27–37 (2008).

    CAS  Article  PubMed  Google Scholar 

  7. 7

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

    CAS  Article  PubMed  Google Scholar 

  8. 8

    Candelli, A., Modesti, M., Peterman, E. J. G. & Wuite, G. J. L. Single-molecule views on homologous recombination. Q. Rev. Biophys. 46, 323–348 (2013).

    CAS  Article  PubMed  Google Scholar 

  9. 9

    Dion, V. & Gasser, S. M. Chromatin movement in the maintenance of genome stability. Cell 152, 1355–1364 (2013).

    CAS  Article  PubMed  Google Scholar 

  10. 10

    Miné-Hattab, J. & Rothstein, R. DNA in motion during double-strand break repair. Trends Cell Biol. 23, 529–536 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. 11

    Camerini-Otero, R. D. & Hsieh, P. Homologous recombination proteins in prokaryotes and eukaryotes. Annu. Rev. Genet. 29, 509–552 (1995).

    CAS  Article  PubMed  Google Scholar 

  12. 12

    Symington, L. S. & Gautier, J. Double-strand break end resection and repair pathway choice. Annu. Rev. Genet. 45, 247–271 (2011).

    CAS  Article  PubMed  Google Scholar 

  13. 13

    Cloud, V., Chan, Y.-L., Grubb, J., Budke, B. & Bishop, D. K. Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis. Science 337, 1222–1225 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Mazin, A. V. & Kowalczykowski, S. C. The specificity of the secondary DNA binding site of RecA protein defines its role in DNA strand exchange. Proc. Natl Acad. Sci. USA 93, 10673–10678 (1996).

    CAS  Article  PubMed  Google Scholar 

  15. 15

    Mazin, A. V. & Kowalczykowski, S. C. The function of the secondary DNA-binding site of RecA protein during DNA strand exchange. EMBO J. 17, 1161–1168 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16

    De Vlaminck, I. et al. Mechanism of homology recognition in DNA recombination from dual-molecule experiments. Mol. Cell 46, 616–624 (2012). A dual molecule manipulation study, which suggests that only a pre-existing single-stranded bubble of the target DNA is bound by the RecA secondary binding site during homology probing.

    CAS  Article  PubMed  Google Scholar 

  17. 17

    Voloshin, O. N. & Camerini-Otero, R. D. Synaptic complex revisited; a homologous recombinase flips and switches bases. Mol. Cell 15, 846–847 (2004).

    CAS  Article  PubMed  Google Scholar 

  18. 18

    Folta-Stogniew, E., O'Malley, S., Gupta, R., Anderson, K. S. & Radding, C. M. Exchange of DNA base pairs that coincides with recognition of homology promoted by E. coli RecA protein. Mol. Cell 15, 965–975 (2004).

    CAS  Article  PubMed  Google Scholar 

  19. 19

    Gupta, R. C., Folta-Stogniew, E., O'Malley, S., Takahashi, M. & Radding, C. M. Rapid exchange of A:T base pairs is essential for recognition of DNA homology by human Rad51 recombination protein. Mol. Cell 4, 705–714 (1999).

    CAS  Article  PubMed  Google Scholar 

  20. 20

    Chen, Z., Yang, H. & Pavletich, N. P. Mechanism of homologous recombination from the RecA–ssDNA/dsDNA structures. Nature 453, 489–484 (2008). Provides the first crystallographic snapshot of RecA–ssDNA and RecA–heteroduplex filaments, and provides evidence for their non-uniform extension.

    CAS  Article  PubMed  Google Scholar 

  21. 21

    Reymer, A., Frykholm, K., Morimatsu, K., Takahashi, M. & Nordén, B. Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy. Proc. Natl Acad. Sci. USA 106, 13248–13253 (2009).

    CAS  Article  PubMed  Google Scholar 

  22. 22

    Savir, Y. & Tlusty, T. RecA-mediated homology search as a nearly optimal signal detection system. Mol. Cell 40, 388–396 (2010).

    CAS  Article  PubMed  Google Scholar 

  23. 23

    Danilowicz, C. et al. The differential extension in dsDNA bound to Rad51 filaments may play important roles in homology recognition and strand exchange. Nucleic Acids Res. 42, 526–533 (2014).

    CAS  Article  PubMed  Google Scholar 

  24. 24

    Danilowicz, C. et al. RecA homology search is promoted by mechanical stress along the scanned duplex DNA. Nucleic Acids Res. 40, 1717–1727 (2012).

    CAS  Article  PubMed  Google Scholar 

  25. 25

    Hsieh, P., Camerini-Otero, C. S. & Camerini-Otero, R. D. The synapsis event in the homologous pairing of DNAs: RecA recognizes and pairs less than one helical repeat of DNA. Proc. Natl Acad. Sci. USA 89, 6492–6496 (1992).

    CAS  Article  PubMed  Google Scholar 

  26. 26

    Sung, P., Krejci, L., van Komen, S. & Sehorn, M. G. Rad51 recombinase and recombination mediators. J. Biol. Chem. 278, 42729–42732 (2003).

    CAS  Article  PubMed  Google Scholar 

  27. 27

    Chi, P., van Komen, S., Sehorn, M. G., Sigurdsson, S. & Sung, P. Roles of ATP binding and ATP hydrolysis in human Rad51 recombinase function. DNA Repair 5, 381–391 (2006).

    CAS  Article  PubMed  Google Scholar 

  28. 28

    Menetski, J. P., Bear, D. G. & Kowalczykowski, S. C. Stable DNA heteroduplex formation catalyzed by the Escherichia coli RecA protein in the absence of ATP hydrolysis. Proc. Natl Acad. Sci. USA 87, 21–25 (1990).

    CAS  Article  PubMed  Google Scholar 

  29. 29

    Sung, P. & Stratton, S. A. Yeast Rad51 recombinase mediates polar DNA strand exchange in the absence of ATP hydrolysis. J. Biol. Chem. 271, 27983–27986 (1996).

    CAS  Article  PubMed  Google Scholar 

  30. 30

    Peacock-Villada, A. et al. Complementary strand relocation may play vital roles in RecA-based homology recognition. Nucleic Acids Res. 40, 10441–10451 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    Ragunathan, K., Joo, C. & Ha, T. Real-time observation of strand exchange reaction with high spatiotemporal resolution. Structure 19, 1064–1073 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32

    Holthausen, J. T., Wyman, C. & Kanaar, R. Regulation of DNA strand exchange in homologous recombination. DNA Repair 9, 1264–1272 (2010).

    CAS  Article  PubMed  Google Scholar 

  33. 33

    Kowalczykowski, S. C. Biochemistry of genetic recombination: energetics and mechanism of DNA strand exchange. Annu. Rev. Biophys. Biophys. Chem. 20, 539–575 (1991).

    CAS  Article  PubMed  Google Scholar 

  34. 34

    Julin, D. A., Riddles, P. W. & Lehman, I. R. On the mechanism of pairing of single- and double-stranded DNA molecules by the recA and single-stranded DNA binding proteins of Escherichia coli. J. Biol. Chem. 261, 1025–1030 (1986).

    CAS  PubMed  Google Scholar 

  35. 35

    Gonda, D. K. & Radding, C. M. By searching processively RecA protein pairs DNA molecules that share a limited stretch of homology. Cell 34, 647–654 (1983).

    CAS  Article  PubMed  Google Scholar 

  36. 36

    Berg, O. G. & Winter, R. B. & von Hippel, P. H. Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory. Biochemistry 20, 6929–6948 (1981).

    CAS  Article  PubMed  Google Scholar 

  37. 37

    Halford, S. E. An end to 40 years of mistakes in DNA–protein association kinetics? Biochem. Soc. Trans. 37, 343–348 (2009).

    CAS  Article  PubMed  Google Scholar 

  38. 38

    Adzuma, K. No sliding during homology search by RecA protein. J. Biol. Chem. 273, 31565–31573 (1998).

    CAS  Article  PubMed  Google Scholar 

  39. 39

    Ragunathan, K., Liu, C. & Ha, T. RecA filament sliding on DNA facilitates homology search. eLife 1, e00067 (2012). Using single-molecule three-colour fluorescence resonance energy transfer (FRET) experiments, this study provides the first evidence for one-dimensional sliding of the presynaptic nucleoprotein filament on target DNA during recombination.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    van der Heijden, T. et al. Homologous recombination in real time: DNA strand exchange by RecA. Mol. Cell 30, 530–538 (2008).

    CAS  Article  PubMed  Google Scholar 

  41. 41

    Forget, A. L. & Kowalczykowski, S. C. Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search. Nature 482, 423–427 (2012). This in vitro study provides a direct visualization of short-lived non-homologous contacts and proposes a crucial role for intersegmental contact sampling in homology recognition.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42

    Zierhut, C. & Diffley, J. F. X. Break dosage, cell cycle stage and DNA replication influence DNA double strand break response. EMBO J. 27, 1875–1885 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43

    White, C. I. & Haber, J. E. Intermediates of recombination during mating type switching in Saccharomyces cerevisiae. EMBO J. 9, 663–673 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44

    Renkawitz, J., Lademann, C. A., Kalocsay, M. & Jentsch, S. Monitoring homology search during DNA double-strand break repair in vivo. Mol. Cell 50, 261–272 (2013). Uses, for the first time, a method that visualizes homology search in vivo . Shows that nuclear organization and spatial proximity are guiding forces for homology search in vivo.

    CAS  Article  PubMed  Google Scholar 

  45. 45

    San Filippo, J., Sung, P. & Klein, H. Mechanism of eukaryotic homologous recombination. Annu. Rev. Biochem. 77, 229–257 (2008).

    CAS  Article  PubMed  Google Scholar 

  46. 46

    Branzei, D. & Foiani, M. Maintaining genome stability at the replication fork. Naure. Rev. Mol. Cell Biol. 11, 208–219 (2010).

    CAS  Article  Google Scholar 

  47. 47

    Loidl, J. The hidden talents of SPO11. Dev. Cell 24, 123–124 (2013).

    CAS  Article  PubMed  Google Scholar 

  48. 48

    Nasmyth, K. & Haering, C. H. Cohesin: its roles and mechanisms. Annu. Rev. Genet. 43, 525–558 (2009).

    CAS  Article  PubMed  Google Scholar 

  49. 49

    Glynn, E. F. et al. Genome-wide mapping of the cohesin complex in the yeast Saccharomyces cerevisiae. PLoS Biol. 2, E259 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Laloraya, S., Guacci, V. & Koshland, D. Chromosomal addresses of the cohesin component Mcd1p. J. Cell Biol. 151, 1047–1056 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. 51

    Chen, B. et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155, 1479–1491 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. 52

    Hoang, M. L. et al. Competitive repair by naturally dispersed repetitive DNA during non-allelic homologous recombination. PLoS Genet. 6, e1001228 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Argueso, J. L. et al. Double-strand breaks associated with repetitive DNA can reshape the genome. Proc. Natl Acad. Sci. USA 105, 11845–11850 (2008).

    CAS  Article  PubMed  Google Scholar 

  54. 54

    Mieczkowski, P. A., Lemoine, F. J. & Petes, T. D. Recombination between retrotransposons as a source of chromosome rearrangements in the yeast Saccharomyces cerevisiae. DNA Repair 5, 1010–1020 (2006).

    CAS  Article  PubMed  Google Scholar 

  55. 55

    Haber, J. E. Transpositions and translocations induced by site-specific double-strand breaks in budding yeast. DNA Repair 5, 998–1009 (2006).

    CAS  Article  PubMed  Google Scholar 

  56. 56

    Agmon, N., Liefshitz, B., Zimmer, C., Fabre, E. & Kupiec, M. Effect of nuclear architecture on the efficiency of double-strand break repair. Nature Cell Biol. 15, 694–699 (2013).

    CAS  Article  PubMed  Google Scholar 

  57. 57

    Coïc, E., Richard, G.-F. & Haber, J. E. Saccharomyces cerevisiae donor preference during mating-type switching is dependent on chromosome architecture and organization. Genetics 173, 1197–1206 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60

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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61

    Haber, J. E. & Leung, W. Y. Lack of chromosome territoriality in yeast: promiscuous rejoining of broken chromosome ends. Proc. Natl Acad. Sci. USA 93, 13949–13954 (1996).

    CAS  Article  PubMed  Google Scholar 

  62. 62

    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 

  63. 63

    Sugawara, N., Wang, X. & Haber, J. E. In vivo roles of Rad52, Rad54, and Rad55 proteins in Rad51-mediated recombination. Mol. Cell 12, 209–219 (2003).

    CAS  Article  PubMed  Google Scholar 

  64. 64

    Misteli, T. & Soutoglou, E. The emerging role of nuclear architecture in DNA repair and genome maintenance. Nature Rev. Mol. Cell Biol. 10, 243–254 (2009).

    CAS  Article  Google Scholar 

  65. 65

    Roukos, V., Burman, B. & Misteli, T. The cellular etiology of chromosome translocations. Curr. Opin. Cell Biol. 25, 357–364 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. 66

    Rocha, P. P. & Skok, J. A. The origin of recurrent translocations in recombining lymphocytes: a balance between break frequency and nuclear proximity. Curr. Opin. Cell Biol. 25, 365–371 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67

    Roukos, V. et al. Spatial dynamics of chromosome translocations in living cells. Science 341, 660–664 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68

    Zhang, Y. et al. Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 148, 908–921 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  69. 69

    Hakim, O. et al. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature 484, 69–74 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70

    Rocha, P. P. et al. Close proximity to Igh is a contributing factor to AID-mediated translocations. Mol. Cell 47, 873–885 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71

    Chiarle, R. et al. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147, 107–119 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72

    Klein, I. A. et al. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147, 95–106 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73

    Roix, J. J., McQueen, P. G., Munson, P. J., Parada, L. A. & Misteli, T. Spatial proximity of translocation-prone gene loci in human lymphomas. Nature Genet. 34, 287–291 (2003).

    CAS  Article  PubMed  Google Scholar 

  74. 74

    Agmon, N., Pur, S., Liefshitz, B. & Kupiec, M. Analysis of repair mechanism choice during homologous recombination. Nucleic Acids Res. 37, 5081–5092 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. 75

    Duan, Z. et al. A three-dimensional model of the yeast genome. Nature 465, 363–367 (2010). The first high-resolution three-dimensional model of the yeast nucleus that provides evidence for the priority of intrachromosomal interactions over interchromosomal interactions and shows that interchromosomal interactions occur preferentially around centromeres.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  76. 76

    Haber, J. E. Mating-type gene switching in Saccharomyces cerevisiae. Annu. Rev. Genet. 32, 561–599 (1998).

    CAS  Article  PubMed  Google Scholar 

  77. 77

    Sugawara, N. & Haber, J. E. Monitoring DNA recombination initiated by HO endonuclease. Methods Mol. Biol. 920, 349–370 (2012).

    CAS  Article  PubMed  Google Scholar 

  78. 78

    Li, J. et al. Regulation of budding yeast mating-type switching donor preference by the FHA domain of Fkh1. PLoS Genet. 8, e1002630 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79

    Wu, X. & Haber, J. E. A 700 bp cis-acting region controls mating-type dependent recombination along the entire left arm of yeast chromosome III. Cell 87, 277–285 (1996).

    CAS  Article  PubMed  Google Scholar 

  80. 80

    Wu, X. & Haber, J. E. MATa donor preference in yeast mating-type switching: activation of a large chromosomal region for recombination. Genes Dev. 9, 1922–1932 (1995).

    CAS  Article  PubMed  Google Scholar 

  81. 81

    Zimmer, C. & Fabre, E. Principles of chromosomal organization: lessons from yeast. J. Cell Biol. 192, 723–733 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  82. 82

    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 

  83. 83

    Wong, H., Arbona, J.-M. & Zimmer, C. How to build a yeast nucleus. Nucleus 4, 361–366 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  84. 84

    Gehlen, L. R., Gasser, S. M. & Dion, V. How broken DNA finds its template for repair: a computational approach. Prog. Theor. Phys. Suppl. 191, 20–29 (2011).

    CAS  Article  Google Scholar 

  85. 85

    Dion, V., Kalck, V., Horigome, C., Towbin, B. D. & Gasser, S. M. Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nature Cell Biol. 14, 502–509 (2012).

    CAS  Article  PubMed  Google Scholar 

  86. 86

    Miné-Hattab, J. & Rothstein, R. Increased chromosome mobility facilitates homology search during recombination. Nature Cell Biol. 14, 510–517 (2012).

    Article  CAS  PubMed  Google Scholar 

  87. 87

    Seeber, A., Dion, V. & Gasser, S. M. Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global chromatin mobility in response to DNA damage. Genes Dev. 27, 1999–2008 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  88. 88

    Dion, V., Kalck, V., Seeber, A., Schleker, T. & Gasser, S. M. Cohesin and the nucleolus constrain the mobility of spontaneous repair foci. EMBO Rep. 14, 984–991 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  89. 89

    Neumann, F. R. et al. Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes Dev. 26, 369–383 (2012). Reports, for the first time, that chromatin has an increased mobility at the site of a DSB and also describes the role of the chromatin remodeller INO80 in this process.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. 90

    Papamichos-Chronakis, M. & Peterson, C. L. Chromatin and the genome integrity network. Nature Rev. Genet. 14, 62–75 (2013).

    CAS  Article  PubMed  Google Scholar 

  91. 91

    Lesterlin, C., Ball, G., Schermelleh, L. & Sherratt, D. J. RecA bundles mediate homology pairing between distant sisters during DNA break repair. Nature 506, 249–253 (2014).

    CAS  Article  PubMed  Google Scholar 

  92. 92

    Ceballos, S. J. & Heyer, W.-D. Functions of the Snf2/Swi2 family Rad54 motor protein in homologous recombination. Biochim. Biophys. Acta 1809, 509–523 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  93. 93

    Mazin, A. V., Bornarth, C. J., Solinger, J. A., Heyer, W. D. & Kowalczykowski, S. C. Rad54 protein is targeted to pairing loci by the Rad51 nucleoprotein filament. Mol. Cell 6, 583–592 (2000).

    CAS  Article  PubMed  Google Scholar 

  94. 94

    Petukhova, G., Stratton, S. & Sung, P. Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins. Nature 393, 91–94 (1998). Demonstrates the importance of Rad54 for Rad51-dependent homologous pairing, which is mediated by direct protein–protein interactions that stimulate the ATPase activity of Rad54.

    CAS  Article  PubMed  Google Scholar 

  95. 95

    Amitani, I., Baskin, R. J. & Kowalczykowski, S. C. Visualization of Rad54, a chromatin remodeling protein, translocating on single DNA molecules. Mol. Cell 23, 143–148 (2006).

    CAS  Article  PubMed  Google Scholar 

  96. 96

    Alexeev, A., Mazin, A. & Kowalczykowski, S. C. Rad54 protein possesses chromatin-remodeling activity stimulated by the Rad51–ssDNA nucleoprotein filament. Nature Struct. Biol. 10, 182–186 (2003).

    CAS  Article  PubMed  Google Scholar 

  97. 97

    Zhang, Z., Fan, H. Y., Goldman, J. A. & Kingston, R. E. Homology-driven chromatin remodeling by human RAD54. Nature Struct. Mol. Biol. 14, 397–405 (2007).

    CAS  Article  Google Scholar 

  98. 98

    Jaskelioff, M., van Komen, S., Krebs, J. E., Sung, P. & Peterson, C. L. Rad54p is a chromatin remodeling enzyme required for heteroduplex DNA joint formation with chromatin. J. Biol. Chem. 278, 9212–9218 (2003).

    CAS  Article  PubMed  Google Scholar 

  99. 99

    Petukhova, G., Sung, P. & Klein, H. Promotion of Rad51-dependent D-loop formation by yeast recombination factor Rdh54/Tid1. Genes Dev. 14, 2206–2215 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  100. 100

    Prasad, T. K. et al. A DNA-translocating Snf2 molecular motor: Saccharomyces cerevisiae Rdh54 displays processive translocation and extrudes DNA loops. J. Mol. Biol. 369, 940–953 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  101. 101

    Nimonkar, A. V., Amitani, I., Baskin, R. J. & Kowalczykowski, S. C. Single molecule imaging of Tid1/Rdh54, a Rad54 homolog that translocates on duplex DNA and can disrupt joint molecules. J. Biol. Chem. 282, 30776–30784 (2007).

    CAS  Article  PubMed  Google Scholar 

  102. 102

    Kwon, Y. et al. ATP-dependent chromatin remodeling by the Saccharomyces cerevisiae homologous recombination factor Rdh54. J. Biol. Chem. 283, 10445–10452 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  103. 103

    Van Komen, S., Petukhova, G., Sigurdsson, S., Stratton, S. & Sung, P. Superhelicity-driven homologous DNA pairing by yeast recombination factors Rad51 and Rad54. Mol. Cell 6, 563–572 (2000).

    CAS  Article  PubMed  Google Scholar 

  104. 104

    Fulconis, R., Mine, J., Bancaud, A., Dutreix, M. & Viovy, J-L. Mechanism of RecA-mediated homologous recombination revisited by single molecule nanomanipulation. EMBO J. 25, 4293–4304 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  105. 105

    Sinha, M. & Peterson, C. L. A Rad51 presynaptic filament is sufficient to capture nucleosomal homology during recombinational repair of a DNA double-strand break. Mol. Cell 30, 803–810 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  106. 106

    Wolner, B. & Peterson, C. L. ATP-dependent and ATP-independent roles for the Rad54 chromatin remodeling enzyme during recombinational repair of a DNA double strand break. J. Biol. Chem. 280, 10855–10860 (2005).

    CAS  Article  PubMed  Google Scholar 

  107. 107

    Hicks, W. M., Yamaguchi, M. & Haber, J. E. Real-time analysis of double-strand DNA break repair by homologous recombination. Proc. Natl Acad. Sci. USA 108, 3108–3115 (2011).

    CAS  Article  PubMed  Google Scholar 

  108. 108

    Wright, W. D. & Heyer, W.-D. Rad54 functions as a heteroduplex DNA pump modulated by its DNA substrates and Rad51 during D loop formation. Mol. Cell 53, 420–432 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  109. 109

    Sinha, M., Watanabe, S., Johnson, A., Moazed, D. & Peterson, C. L. Recombinational repair within heterochromatin requires ATP-dependent chromatin remodeling. Cell 138, 1109–1121 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  110. 110

    Tsabar, M. & Haber, J. E. Chromatin modifications and chromatin remodeling during DNA repair in budding yeast. Curr. Opin. Genet. Dev. 23, 166–173 (2013).

    CAS  Article  PubMed  Google Scholar 

  111. 111

    Tsukuda, T. et al. INO80-dependent chromatin remodeling regulates early and late stages of mitotic homologous recombination. DNA Repair 8, 360–369 (2009).

    CAS  Article  PubMed  Google Scholar 

  112. 112

    Chai, B., Huang, J., Cairns, B. R. & Laurent, B. C. Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair. Genes Dev. 19, 1656–1661 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  113. 113

    Iacovoni, J. S. et al. High-resolution profiling of γH2AX around DNA double strand breaks in the mammalian genome. EMBO J. 29, 1446–1457 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  114. 114

    Strom, L., Lindroos, H. B., Shirahige, K. & Sjogren, C. Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair. Mol. Cell 16, 1003–1015 (2004).

    Article  PubMed  Google Scholar 

  115. 115

    Renkawitz, J., Lademann, C. A. & Jentsch, S. γH2AX spreading linked to homology search. Cell Cycle 12, 2526–2527 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  116. 116

    Lee, C.-S., Lee, K., Legube, G. & Haber, J. E. Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break. Nature Struct. Mol. Biol. 21, 103–109 (2014).

    CAS  Article  Google Scholar 

  117. 117

    Bennett, G., Papamichos-Chronakis, M. & Peterson, C. L. DNA repair choice defines a common pathway for recruitment of chromatin regulators. Nature Commun. 4, 2084 (2013).

    Article  CAS  Google Scholar 

  118. 118

    Hirano, T. At the heart of the chromosome: SMC proteins in action. Nature Rev. Mol. Cell Biol. 7, 311–322 (2006).

    CAS  Article  Google Scholar 

  119. 119

    Merkenschlager, M. & Odom, D. T. CTCF and cohesin: linking gene regulatory elements with their targets. Cell 152, 1285–1297 (2013).

    CAS  Article  PubMed  Google Scholar 

  120. 120

    Sjogren, C. & Nasmyth, K. Sister chromatid cohesion is required for postreplicative double-strand break repair in Saccharomyces cerevisiae. Curr. Biol. 11, 991–995 (2001).

    CAS  Article  PubMed  Google Scholar 

  121. 121

    Unal, E., Heidinger-Pauli, J. M. & Koshland, D. DNA double-strand breaks trigger genome-wide sister-chromatid cohesion through Eco1 (Ctf7). Science 317, 245–248 (2007).

    Article  CAS  PubMed  Google Scholar 

  122. 122

    Strom, L. et al. Postreplicative formation of cohesion is required for repair and induced by a single DNA break. Science 317, 242–245 (2007).

    Article  CAS  PubMed  Google Scholar 

  123. 123

    Sonoda, E. et al. Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells. Dev. Cell 1, 759–770 (2001).

    CAS  Article  PubMed  Google Scholar 

  124. 124

    Unal, E. et al. DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol. Cell 16, 991–1002 (2004).

    Article  PubMed  Google Scholar 

  125. 125

    De Piccoli, G. et al. Smc5–Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nature Cell Biol. 8, 1032–1034 (2006).

    CAS  Article  PubMed  Google Scholar 

  126. 126

    Potts, P. R., Porteus, M. H. & Yu, H. Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J. 25, 3377–3388 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  127. 127

    Covo, S., Westmoreland, J. W., Gordenin, D. A. & Resnick, M. A. Cohesin is limiting for the suppression of DNA damage-induced recombination between homologous chromosomes. PLoS Genet. 6, e1001006 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. 128

    Coïc, E. et al. Dynamics of homology searching during gene conversion in Saccharomyces cerevisiae revealed by donor competition. Genetics 189, 1225–1233 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. 129

    Gibcus, J. H. & Dekker, J. The hierarchy of the 3D genome. Mol. Cell 49, 773–782 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  130. 130

    White, R. R. et al. Double-strand break repair by interchromosomal recombination: an in vivo repair mechanism utilized by multiple somatic tissues in mammals. PLoS ONE 8, e84379 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. 131

    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 

  132. 132

    Chiolo, I. et al. Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell 144, 732–744 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  133. 133

    Jakob, B. et al. DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin. Nucleic Acids Res. 39, 6489–6499 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  134. 134

    Kim, J.-A., Kruhlak, M., Dotiwala, F., Nussenzweig, A. & Haber, J. E. Heterochromatin is refractory to γ-H2AX modification in yeast and mammals. J. Cell Biol. 178, 209–218 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  135. 135

    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).

    CAS  Article  PubMed  Google Scholar 

  136. 136

    Shen, P. & Huang, H. V. Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics 112, 441–457 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137

    Ira, G. & Haber, J. E. Characterization of RAD51-independent break-induced replication that acts preferentially with short homologous sequences. Mol. Cell. Biol. 22, 6384–6392 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  138. 138

    Shulman, M. J., Nissen, L. & Collins, C. Homologous recombination in hybridoma cells: dependence on time and fragment length. Mol. Cell. Biol. 10, 4466–4472 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  139. 139

    Hasty, P., Rivera-Pérez, J. & Bradley, A. The length of homology required for gene targeting in embryonic stem cells. Mol. Cell. Biol. 11, 5586–5591 (1991).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  140. 140

    Mundia, M. M., Desai, V., Magwood, A. C. & Baker, M. D. Nascent DNA synthesis during homologous recombination is synergistically promoted by the Rad51 recombinase and DNA homology. Genetics http://dx.doi.org/10.1534/genetics.114.161455 (2014).

  141. 141

    Ira, G., Malkova, A., Liberi, G., Foiani, M. & Haber, J. E. Srs2 and Sgs1–Top3 suppress crossovers during double-strand break repair in yeast. Cell 115, 401–411 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  142. 142

    Nagai, S. et al. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science 322, 597–602 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  143. 143

    Kalocsay, M., Hiller, N. J. & Jentsch, S. Chromosome-wide Rad51 spreading and SUMO–H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol. Cell 33, 335–343 (2009).

    CAS  Article  PubMed  Google Scholar 

  144. 144

    Oza, P., Jaspersen, S. L., Miele, A., Dekker, J. & Peterson, C. L. Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev. 23, 912–927 (2009).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  145. 145

    Alt, F. W., Zhang, Y., Meng, F.-L., Guo, C. & Schwer, B. Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell 152, 417–429 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  146. 146

    Schatz, D. G. & Ji, Y. Recombination centres and the orchestration of V(D)J recombination. Nature Rev. Immunol. 11, 251–263 (2011).

    CAS  Article  Google Scholar 

  147. 147

    Brisson, D., Drecktrah, D., Eggers, C. H. & Samuels, D. S. Genetics of Borrelia burgdorferi. Annu. Rev. Genet. 46, 515–536 (2012).

    CAS  Article  PubMed  Google Scholar 

  148. 148

    Cahoon, L. A. & Seifert, H. S. Focusing homologous recombination: pilin antigenic variation in the pathogenic Neisseria. Mol. Microbiol. 81, 1136–1143 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  149. 149

    Glover, L. et al. Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control. Cell. Microbiol. 15, 1984–1993 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  150. 150

    Guizetti, J. & Scherf, A. Silence, activate, poise and switch! Mechanisms of antigenic variation in Plasmodium falciparum. Cell. Microbiol. 15, 718–726 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  151. 151

    Jurka, J., Kapitonov, V. V., Kohany, O. & Jurka, M. V. Repetitive sequences in complex genomes: structure and evolution. Annu. Rev. Genom. Hum. Genet. 8, 241–259 (2007).

    CAS  Article  Google Scholar 

  152. 152

    Stracker, T. H. & Petrini, J. H. The MRE11 complex: starting from the ends. Nature Rev. Mol. Cell Biol. 12, 90–103 (2011).

    CAS  Article  Google Scholar 

  153. 153

    Liu, J., Sneeden, J. & Heyer, W.-D. In vitro assays for DNA pairing and recombination-associated DNA synthesis. Methods Mol. Biol. 745, 363–383 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  154. 154

    Bazemore, L. R., Takahashi, M. & Radding, C. M. Kinetic analysis of pairing and strand exchange catalyzed by RecA. Detection by fluorescence energy transfer. J. Biol. Chem. 272, 14672–14682 (1997).

    CAS  Article  PubMed  Google Scholar 

  155. 155

    Mani, A., Braslavsky, I., Arbel-Goren, R. & Stavans, J. Caught in the act: the lifetime of synaptic intermediates during the search for homology on DNA. Nucleic Acids Res. 38, 2036–2043 (2010).

    CAS  Article  PubMed  Google Scholar 

  156. 156

    Forget, A. L. & Kowalczykowski, S. C. Single-molecule imaging brings Rad51 nucleoprotein filaments into focus. Trends Cell Biol. 20, 269–276 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  157. 157

    Rouet, P., Smih, F. & Jasin, M. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol. Cell. Biol. 14, 8096–8106 (1994).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  158. 158

    Kramer, K. M., Brock, J. A., Bloom, K., Moore, J. K. & Haber, J. E. Two different types of double-strand breaks in Saccharomyces cerevisiae are repaired by similar RAD52-independent, nonhomologous recombination events. Mol. Cell. Biol. 14, 1293–1301 (1994).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  159. 159

    Bickmore, W. A. & van Steensel, B. Genome architecture: domain organization of interphase chromosomes. Cell 152, 1270–1284 (2013).

    CAS  Article  PubMed  Google Scholar 

  160. 160

    Sharma, R. & Meister, P. Nuclear organization in the nematode C. elegans. Curr. Opin. Cell Biol. 25, 395–402 (2013).

    CAS  Article  PubMed  Google Scholar 

  161. 161

    Wang, X., Montero Llopis, P. & Rudner, D. Z. Organization and segregation of bacterial chromosomes. Nature Rev. Genet. 14, 191–203 (2013).

    CAS  Article  PubMed  Google Scholar 

  162. 162

    O'Sullivan, J. M. Yeast chromosomal interactions and nuclear architecture. Curr. Opin. Cell Biol. 22, 298–304 (2010).

    CAS  Article  PubMed  Google Scholar 

  163. 163

    Olsson, I. & Bjerling, P. Advancing our understanding of functional genome organisation through studies in the fission yeast. Curr. Genet. 57, 1–12 (2011).

    CAS  Article  PubMed  Google Scholar 

  164. 164

    Cremer, T. & Cremer, M. Chromosome territories. Cold Spring Harb. Perspect. Biol. 2, a003889 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. 165

    Cremer, T. & Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Rev. Genet. 2, 292–301 (2001).

    CAS  Article  PubMed  Google Scholar 

  166. 166

    Schermelleh, L., Heintzmann, R. & Leonhardt, H. A guide to super-resolution fluorescence microscopy. J. Cell Biol. 190, 165–175 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  167. 167

    Dekker, J., Marti-Renom, M. A. & Mirny, L. A. Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nature Rev. Genet. 14, 390–403 (2013).

    CAS  Article  PubMed  Google Scholar 

  168. 168

    van Steensel, B. & Dekker, J. Genomics tools for unraveling chromosome architecture. Nature Biotech. 28, 1089–1095 (2010).

    CAS  Article  Google Scholar 

  169. 169

    Cavalli, G. & Misteli, T. Functional implications of genome topology. Nature Struct. Mol. Biol. 20, 290–299 (2013).

    CAS  Article  Google Scholar 

  170. 170

    Geyer, P. K., Vitalini, M. W. & Wallrath, L. L. Nuclear organization: taking a position on gene expression. Curr. Opin. Cell Biol. 23, 354–359 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  171. 171

    Sexton, T., Schober, H., Fraser, P. & Gasser, S. M. Gene regulation through nuclear organization. Nature Struct. Mol. Biol. 14, 1049–1055 (2007).

    CAS  Article  Google Scholar 

  172. 172

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

    CAS  Article  PubMed  Google Scholar 

  173. 173

    Berger, A. B. et al. High-resolution statistical mapping reveals gene territories in live yeast. Nature Methods 5, 1031–1037 (2008).

    CAS  Article  PubMed  Google Scholar 

  174. 174

    Bystricky, K., Laroche, T., van Houwe, G., Blaszczyk, M. & Gasser, S. M. Chromosome looping in yeast: telomere pairing and coordinated movement reflect anchoring efficiency and territorial organization. J. Cell Biol. 168, 375–387 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  175. 175

    Wong, H. et al. A predictive computational model of the dynamic 3D interphase yeast nucleus. Curr. Biol. 22, 1881–1890 (2012).

    CAS  Article  PubMed  Google Scholar 

  176. 176

    Tjong, H., Gong, K., Chen, L. & Alber, F. Physical tethering and volume exclusion determine higher-order genome organization in budding yeast. Genome Res. 22, 1295–1305 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

S.J. is supported by the Max Planck Society, Deutsche Forschungsgemeinschaft, Center for Integrated Protein Science Munich, RUBICON EU Network of Excellence, European Research Council (ERC) Advanced Grant and the Louis-Jeantet Foundation. J.R. was supported by a Boehringer Ingelheim Fonds PhD stipend.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Stefan Jentsch.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Mating-type switching

A process by which yeast cells switch their mating-type through programmed homologous recombination.

Strand exchange

A continuous establishment of base pairing between the recombinase-coated single-stranded DNA (ssDNA), at the DNA double-strand break (DSB), and the complementary strand of the homologous DNA.

Heteroduplex

Double-stranded DNA that consists of two single DNA strands of different origin.

B-DNA

Standard conformation of DNA as it exists in most functional organisms.

Repetitive elements

Genetic elements, such as satellite DNA or retrotransposons, that are present in multiple copies in a genome and/or consist of small repetitive building blocks.

Ectopic homologous recombination

Recombination with a homologous sequence that is located in a genomic location other than the corresponding allele on the sister chromatid or homologous chromosome.

Recombination enhancer

A specific sequence that is present in the genome of the yeast Saccharomyces cerevisiae, which enables the establishment of a large chromosomal loop to facilitate recombination in cells of mating-type a (MATa).

Chromosome conformation capture

A method to analyze the spatial interaction frequency of either selected genomic loci or of loci on a genome-wide level. It is based on the chemical crosslinking of samples, which is followed by their restriction digest and a subsequent ligation procedure.

Displacement loop

(D-loop). A structure in which the two strands of a DNA duplex are separated by the binding of a third strand to one of these strands.

ATP-dependent chromatin remodelling complexes

Protein complexes that use the energy of ATP to reposition nucleosomes, evict histones or incorporate new histone variants.

Structural maintenance of chromosome proteins

(SMC proteins). A conserved ATPase protein family that coordinates many aspects of chromosome organization, for example sister-chromatid cohesion and chromosome condensation in mitosis.

V(D)J recombination

Combination of variable (V), diverse (D) and joining(J) gene segments during a programmed recombination event in lymphoid cells to form diverse immunoglobulins and T cell receptors.

Class switch recombination

Programmed recombination in B lymphocytes to generate different antibody subtypes with the same antigen specificity.

Surface protein gene arrangements

A mechanism that enables some pathogens to evade the host adaptive immune system by altering their immunogenic epitopes (antigenic variation) through recombination-mediated switching between several different surface protein variants.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Renkawitz, J., Lademann, C. & Jentsch, S. Mechanisms and principles of homology search during recombination. Nat Rev Mol Cell Biol 15, 369–383 (2014). https://doi.org/10.1038/nrm3805

Download citation

Further reading

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing