Skip to main content
SpringerLink
Log in

Main repair pathways of double-strand breaks in the genomic DNA and interactions between them

  • Published:
Cytology and Genetics Aims and scope Submit manuscript

Abstract

Double-strand DNA breaks (DSBs) resulting from metabolic cellular processes and external factors pose a serious threat to the stability of the genome, but the cells have molecular mechanisms for the efficient repair of this type of damage. In this review, we examine two main biochemical pathways of repairing the double-strand DNA breaks in eukaryotic cells—DNA strands nonhomologous end joining and homologous recombination between sister chromatids or chromatids of homologous chromosomes. Numerous data obtained recently for various eukaryotic cells suggest that there is a complex interplay between the main DSB repair pathways, which normally facilitates efficient repair and maintenance of the structural and functional integrity of the genome, but which, at the same time, under conditions of exposure to genotoxic factors may induce increased genomic instability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kovaleva, O.A., Cytogenetic anomalies and causes for their occurrence in somatic cells, Cytol. Genet., 2008, vol. 42, no. 1, pp. 48–59.

    Article  Google Scholar 

  2. Acilan, C., Potter, D., and Saunders, W., DNA repair pathways involved in anaphase bridge formation, Genes. Chrom. Cancer, 2007, vol. 46, no. 6, pp. 522–531.

    Article  CAS  PubMed  Google Scholar 

  3. Ferguson, D., Sekiguchi, J., Chang, S., et al., The nonhomologous end-joining pathway of dna repair is required for genomic stability and the suppression of translocations, Proc. Natl. Acad. Sci. U.S.A., 2000, vol. 97, no. 12, pp. 6630–6633.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Iliakis, G., Wu, W., Wang, M., et al., Backup pathways of nonhomologous end joining may have a dominant role in the formation of chromosome aberrations, in Chromosomal Alterations, Obe, G., et al., Eds., Berlin: Springer Verlag, 2007, pp. 67–85.

    Chapter  Google Scholar 

  5. Mills, K., Ferguson, D., and Alt, F., The role of DNA breaks in genomic instability and tumorigenesis, Immun. Rev., 2003, vol. 194, pp. 77–95.

    Article  CAS  PubMed  Google Scholar 

  6. Schwartz, M., Zlotorynski, E., Goldberg, M., et al., Homologous recombination and nonhomologous end-joining repair pathways regulate fragile site stability, Genes Dev., 2005, vol. 19, pp. 2715–2726.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Takata, M., Sasaki, M., Sonoda, E., et al., Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells, EMBO J., 1998, vol. 17, no. 18, pp. 5497–5508.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Bennardo, N., Gunn, A., Cheng, A., et al., Limiting the persistence of a chromosome break diminishes its mutagenic potential, PLoS Genet., 2009, vol. 5, no. 10, p. e1000683.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Gandhi, M., Evdokimova, V., Cuenco, K., et al., Homologous chromosomes make contact at the sites of double-strand breaks in genes in somatic G0/G1-phase human cells, Proc. Natl. Acad. Sci. U.S.A., 2012, vol. 109, no. 24, pp. 9454–9459.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Meulle, A., Salles, B., Le Daviaud, D., et al., Positive regulation of DNA double strand break repair activity during differentiation of long span cells: the example of adipogenesis, PLoS One, 2008, vol. 3, no. 10, p. e3345.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Ciccia, A. and Eleldge, S., The DNA damage response: making it safe to play with knives, Mol. Cell, 2010, vol. 40, pp. 179–204.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. DNA Repair, Kruman, I., Ed., Rijeka: InTech, 2011.

    Google Scholar 

  13. Hiom, K., Coping with DNA double strand breaks, DNA Rep., 2010, vol. 9, no. 12, pp. 1256–1263.

    Article  CAS  Google Scholar 

  14. Pardo, B., Gymez-González, B., and Aguilera, A., DNA double-strand break repair: how to fix a broken relationship, Cell. Mol. Life Sci., 2009, vol. 66, no. 6, pp. 1039–1056.

    Article  CAS  PubMed  Google Scholar 

  15. Bogomazova, A., Lagarkova, M., Tskhovrebova, L., et al., Error-prone nonhomologous end joining repair operates in human pluripotent stem cells during late G2, Aging, 2011, vol. 3, no. 6, pp. 584–596.

    PubMed Central  PubMed  Google Scholar 

  16. Hefferin, M. and Tomkinson, A., Mechanism of dna double-strand break repair by non-homologous end joining, DNA Rep., 2005, vol. 4, no. 6, pp. 639–648.

    Article  CAS  Google Scholar 

  17. Lieber, M., The mechanism of double-strand DNA break repair by the nonhomologous DNA end joining pathway, Annu. Rev. Biochem., 2010, vol. 79, pp. 181–211.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Mladenov, E. and Iliakis, G., DNA Repair—On the Pathways to Fixing DNA Damage and Errors, Storici, Fr., Ed., Fijeka: InTech, 2011.

  19. Jackson, S., Sensing and repairing dna double-strand breaks, Carcinogenesis, 2002, vol. 23, no. 5, pp. 687–696.

    Article  CAS  PubMed  Google Scholar 

  20. Yang, J., Xu, Z.-P., Huang, Y., et al., ATM and ATR: sensing DNA damage, World J. Gastroenterol., 2004, vol. 10, no. 2, pp. 155–160.

    CAS  PubMed  Google Scholar 

  21. Kass, E. and Jasin, M., Collaboration and competition between DNA double-strand break repair pathways, FEBS Lett., 2010, vol. 584, no. 17, pp. 3703–3708.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Lin, Y., P63 and p73 transcriptionally regulate genes involved in DNA repair, PLoS Genet., 2009, vol. 5, no. 10, p. e1000680.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Suzuki, K., Takahashi, M., Oka, Y., et al., Requirement of ATM-dependent pathway for the repair of a subset of DNA double strand breaks created by restriction endonucleases, Genome Integr., 2010, vol. 1, no. 4, p. 11.

    Google Scholar 

  24. Rahal, E., Henricksen, L., Li, Y., et al., AMT regulates Mre11-dependent DNA end-degradation and microhomology-mediated and joining, Cell Cycle, 2010, vol. 9, no. 4, pp. 2866–2877.

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Yamauchi, M., Suzuki, K., Oka, Y., et al., Mode of ATM-dependent suppression of chromosome translocation, Biochem. Biophys. Res. Commun., 2011, vol. 416, nos. 1/2, pp. 111–118.

    Article  CAS  Google Scholar 

  26. Tuteja, N., Singh, M., Misra, M., et al., Molecular mechanisms of DNA damage and repair: progress in plants, Crit. Rev. Biochem. Mol. Biol., 2001, vol. 36, no. 4, pp. 337–397.

    Article  CAS  PubMed  Google Scholar 

  27. Vonarx, E., The repair and tolerance of DNA damage in higher plants, PhD Thesis, Deakin Univ., 2000.

    Google Scholar 

  28. Ataian, Y. and Krebs, J., Five repair pathways in one context: chromatin modification during DNA repair, Biochem. Cell Biol., 2006, vol. 84, no. 4, pp. 490–504.

    Article  CAS  PubMed  Google Scholar 

  29. Rosidi, B., Wang, M., Wu, W., et al., Histone H1 functions as a stimulatory factor in backup pathways of NHEJ, Nucleic Acids Res., 2008, vol. 36, no. 5, pp. 1610–1623.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Roberts, S., Strande, N., Burkhalter, M., et al., Ku is a 5’dRP/AP lyase that excises nucleotide damage near broken ends, Nature, 2010, vol. 464, pp. 1214–1217.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Fu, B.V., The role of DNA polymerase 4 in homologous recombination, UC Davis Undergrad. Res. J., 2011, vol. 14.

  32. Lehman, J., Hoelz, D., and Turchi, J., DNA-dependent conformational changes in the Ku heterodimer, Biochemistry, 2008, vol. 47, no. 15, pp. 4359–4368.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Adams, B., Hawkins, A., Povirk, L., et al., ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells, Aging, 2010, vol. 2, no. 9, pp. 582–596.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Guirouilh-Barbat, J., Raas, E., Plo, I., et al., Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends, Proc. Natl. Acad. Sci. U.S.A., 2007, vol. 104, no. 52, pp. 20902–20907.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Windhofer, F., Wu, W., and Iliakis, G., Low levels of DNA ligases III and IV sufficient for effective NHEJ, J. Cell Physiol., 2007, vol. 213, no. 2, pp. 475–483.

    Article  CAS  PubMed  Google Scholar 

  36. Lieber, M., The mechanism of human nonhomologous DNA end joining, J. Biol. Chem., 2008, vol. 283, no. 1, pp. 1–5.

    Article  CAS  PubMed  Google Scholar 

  37. Yano, K., Morotomi-Yano, K., Adachi, N., et al., Molecular mechanism of protein assembly on DNA double-strand breaks in the non-homologous endjoining pathway, J. Radiat. Res., 2009, vol. 50, no. 2, pp. 97–108.

    Article  CAS  PubMed  Google Scholar 

  38. Belousova, E. and Lavrik, O., DNA polymerases β and λ and their roles in DNA Replication and Repair, Mol. Biol. (Moscow), 2010, vol. 44, no. 6, pp. 839–855.

    Article  CAS  Google Scholar 

  39. Crespan, E., Czabany, T., Maga, G., et al., Microhomology-mediated DNA strand annealing and elongation by human DNA polymerases and on normal and repetitive DNA sequences, Nucleic Acids Res., 2012, vol. 40, no. 12, pp. 5577–5590.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Hogg, M., Sauer-Eriksson, E., and Johansson, E., Promiscuous DNA synthesis by human DNA polymerase, Nucleic Acids Res., 2012, vol. 40, no. 6, pp. 2611–2622.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Brady, N., Gaymes, T., Cheung, M., et al., Increased error-prone NHEJ activity in myeloid leukemias is associated with DNA damage at sites that recruit key nonhomologous end-joining proteins, Cancer Res., 2003, vol. 63, no. 8, pp. 1798–1805.

    CAS  PubMed  Google Scholar 

  42. Hartlerode, A. and Scully, R., Mechanisms of doublestrand break repair in somatic mammalian cells, Biochem. J., 2009, vol. 423, no. 2, pp. 157–168.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Adachi, N., Ishino, T., Ishii, Y., et al., DNA ligase ivdeficient cells are more resistant to ionizing radiation in the absence of Ku70: implications for DNA doublestrand break repair, Proc. Natl. Acad. Sci. U.S.A., 2001, vol. 98, no. 21, pp. 12109–12113.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Decottignies, A., Capture of extranuclear DNA at fission yeast double-strand breaks, Genetics, 2005, vol. 171, pp. 1535–1548.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Jia, Q., DNA repair and gene targeting in plant endjoining mutants, PhD Thesis, Leiden Univ., 2011.

    Google Scholar 

  46. Li, P., Li, J., Li, M., et al., Multiple end-joining mechanisms repair a chromosomal DNA break in fission yeast, DNA Rep., 2011, vol. 11, no. 2, pp. 120–130.

    Article  CAS  Google Scholar 

  47. Prudden, J., Evans, J., Hussey, S., et al., Pathway utilization in response to a site-specific DNA doublestrand break in fission yeast, EMBO J., 2003, vol. 22, no. 6, pp. 1419–1430.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Weinstock, D. and Jasin, M., Alternative pathways for the repair of rag-induced DNA breaks, Mol. Cell. Biol., 2006, vol. 26, no. 1, pp. 131–139.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Bennardo, N., Cheng, A., Huang, N., et al., Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair, PLoS Genet., 2008, vol. 4, no. 6, p. e1000110.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Manova, V., Processing of DNA double strand breaks by alternative non-homologous end-joining in hyperacetylated chromatin, Genome Integr., 2012, vol. 3, no. 4, p. 15.

    Google Scholar 

  51. Cheng, Q., Barboule, N., Frit, P., et al., Ku counteracts mobilization of parp1 and MRN in chromatin damaged with DNA double-strand breaks, Nucleic Acids Res., 2011, vol. 39, no. 22, pp. 9605–9619.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Della-Maria, J., Zhou, Y., Tsai, M., et al., Human Mre11/Human Rad50/Nbs1 and DNA ligase IIIalpha/XRCC1 protein complexes act together in an alternative non-homologous end joining pathway, J. Biol. Chem., 2011, vol. 286, no. 39, pp. 33845–33853.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Loser, D., Investigating the mechanisms by which PARP inhibitors increase sensitivity to DNA damaging agents, PhD Thesis, Univ. of Sussex, 2009.

    Google Scholar 

  54. Mansour, W., Rhein, T., and Dahm-Daphi, J., The alternative end-joining pathway for repair of DNA double-strand breaks requires parp1 but is not dependent upon microhomologies, Nucleic Acids Res., 2010, vol. 38, no. 18, pp. 6065–6077.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Quennet, V., Beucher, A., Baton, O., et al., CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1, Nucleic Acids Res., 2011, vol. 39, no. 6, pp. 2144–2152.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Taylor, E., Cecillon, S., Bonis, A., et al., The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis, Nucleic Acids Res., 2010, vol. 38, no. 2, pp. 441–454.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Wang, M., Wu Weizhong, Wu Wenqi, et al., PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways, Nucleic Acids Res., 2006, vol. 34, no. 21, pp. 6170–6182.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Haber, J., Alternative endings, Proc. Natl. Acad. Sci. U.S.A., 2008, vol. 105, no. 2, pp. 405–406.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Chapman, R., Taylor, M., and Boulton, S., Playing the end game: DNA double-strand break repair pathway choice, Mol. Cell, 2012, vol. 47, no. 4, pp. 497–510.

    Article  CAS  PubMed  Google Scholar 

  60. Majka, J., Alford, B., Ausio, J., et al., ATP hydrolysis by RAD50 switches MRE11 from an endonuclease to an exonuclease, J. Biol. Chem., 2012, vol. 287, no. 4, pp. 2328–2341.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Paull, T., Making the best of the loose ends: Mre11/Rad50 complexes and sae2 promote DNA double-strand break resection, DNA Repair, 2010, vol. 9, no. 12, pp. 1283–1291.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Mannuss, A., Dukowic-Schulze, S., Suer, S., et al., RAD5A, RECQ4A, and MUS81 have specific functions in homologous recombination and define different pathways of DNA repair in Arabidopsis thaliana, Plant Cell, 2010, vol. 22, no. 10, pp. 3318–3330.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. McVey, M., Radut, D., and Sekelsky, J., End-joining repair of double-strand breaks in drosophila melanogaster is largely DNA ligase iv independent, Genetics, 2004, vol. 168, no. 4, pp. 2067–2076.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Li, X. and Heyer, W., Homologous recombination in DNA repair and DNA damage tolerance, Cell Res., 2008, vol. 18, no. 1, pp. 99–113.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Wang, H., Shao, Z., Shi, L., et al., CtIP dimerization is critical for its recruitment to chromosomal DNA double-strand breaks, J. Biol. Chem., 2012, vol. 287, no. 25, pp. 21471–21480.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Wang, B., BRCA2 tumor suppressor network: focusing on its tail, Cell Biosci., 2012, vol. 2, no. 6. doi 10.1186/2045-3701-2-6

    Google Scholar 

  67. Yun, M. and Hiom, K., Ctlp-brca1 modulates the choice of DNA double strand-break repair pathway throughout the cell cycle, Nature, 2009, vol. 459, pp. 460–463.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Grabarz, A., Barascu, A., Guirouilh-Barbat, J., et al., Initiation of DNA double strand break repair: signaling and single-stranded resection dictate the choice between homologous recombination, non-homologous end-joining and alternative end-joining, Am. J. Cancer Res., 2012, vol. 2, no. 3, pp. 249–268.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Chittela, R. and Sainis, J., Plant DNA recombinases: a long way to go, J. Nucl. Acids, 2010. doi 10.4061/2010/646109

    Google Scholar 

  70. Ma, J.-L., Kim, E., Haber, J., et al., Yeast mre11 and rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences, Mol. Cell. Biol., 2003, vol. 23, no. 23, pp. 8820–8828.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Wu, X., Wilson, T., and Lieber, M., A role for fen-1 in nonhomologous DNA end joining: the order of strand annealing and nucleolytic processing events, Proc. Natl. Acad. Sci. U.S.A., 1999, vol. 96, no. 4, pp. 1303–1308.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Tichy, E., Pillai, R., Deng, L., et al., Mouse embryonic stem cells, but not somatic cells, predominantly use homologous recombination to repair double-strand DNA breaks, Stem Cells Dev., 2010, vol. 19, no. 11, pp. 1699–1711.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Shrivastav, M., De Haro, L., and Nickoloff, J., Regulation of DNA double-strand break repair pathway choice, Cell Res., 2008, vol. 18, no. 1, pp. 134–147.

    Article  CAS  PubMed  Google Scholar 

  74. Semenova, E., Filatov, M., Shtamm, T., and Varfolomeeva, E., Human RAD51 recombinase: the role in the cell cycle checkpoint and cellular survival, Tsitologiia, 2008, no. 11, pp. 959–963.

    Google Scholar 

  75. Guirouilh-Barbat, J., Huck, S., Bertrand, P., et al., Impact of the Ku80 pathway on nhej-induced genome rearrangements in mammalian cells, Mol. Cell, 2004, vol. 14, no. 5, pp. 611–623.

    Article  CAS  PubMed  Google Scholar 

  76. Simsek, D., Brunet, E., Wong, S., et al., DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation, PLoS Genet., 2011, vol. 7, no. 6, pp. 1–11.

    Article  CAS  Google Scholar 

  77. Burkhalter, M., Roberts, S., Havener, J., et al., Activity of ribonucleotide reductase helps determine how cells repair DNA double strand breaks, DNA Rep., 2009, vol. 8, no. 11, pp. 1258–1263.

    Article  CAS  Google Scholar 

  78. Rothkamm, K., Kruger, I., Thompson, L., et al., Pathways of DNA double-strand break repair during the mammalian cell cycle, Mol. Cell. Biol., 2003, vol. 23, no. 16, pp. 5706–5715.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Boboila, C., Oksenych, V., Gostissa, M., et al., Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1), Proc. Natl. Acad. Sci. U.S.A., 2013, vol. 110, no. 14, pp. 5731–5738.

    Google Scholar 

  80. Decottingnies, A., Microhomology-mediated end joining in fission yeast is repressed by Pku70 and relies on genes involved in homologous recombination, Genetics, 2007, vol. 176, no. 3, pp. 1403–1415.

    Article  CAS  Google Scholar 

  81. Fattah, F., Lee, E., Weisensel, N., et al., Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells, PLoS Genet., 2010, vol. 6, no. 2. doi 10.1371/journal.pgen.1000855

    Google Scholar 

  82. McVey, M. and Lee, S., MMEJ repair of double-strand breaks (director’s cut): deleted sequences and alternative endings, Trends Genet., 2008, vol. 24, no. 11, pp. 529–538.

    Article  CAS  PubMed  Google Scholar 

  83. Wang, H., Perrault, A., Takeda, Y., et al., Biochemical evidence for Ku-independent backup pathways of NHEJ, Nucleic Acids Res., 2003, vol. 31, no. 18, pp. 5377–5388.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Kotlovaya, N., Activation of repair and checkpoint control by double-strand DNA breaks. Protein phosphorylation activation cascade, Preprint of the Joint Institute for Nuclear Research, Dubna, 2007. http://www1.jinr.ru/Preprints/2007/132%28P19-2007-132%29.pdf

    Google Scholar 

  85. Peterson, S., Li, Y., Chait, B., et al., Cdk1 uncouples CtIP-dependent resection and Rad51 filament formation during M-phase double-strand break repair, J. Cell Biol., 2011, vol. 194, no. 5, pp. 705–720.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Summers, K.C., Shen, F., Sierra Potchanant, E.A., et al., Phosphorylation: the molecular switch of double-strand break repair, Int. J. Proteomics, 2011. doi 10.1155/011/373816

    Google Scholar 

  87. De Zio, D., Bordi, M., and Cecconi, F., Oxidative DNA damage in neurons: implication of Ku in neuronal homeostasis and survival, Int. J. Cell Biol., 2012.

    Google Scholar 

  88. Kanungo, J., DNA repair defects and DNA-PK in neurodegeneration, Cell Dev. Biol., 2012, vol. 1, no. 2, p. 1000e105.

    Article  Google Scholar 

  89. Orii, K., Lee, Y., Kondo, N., et al., Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development, Proc. Natl. Acad. Sci. U.S.A., 2006, vol. 103, no. 26, pp. 10017–10022.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Shibata, A., Conrad, S., Birraux, J., et al., Factors determining DNA double-strand break repair pathway choice in G2 phase, EMBO J., 2011, vol. 30, no. 6, pp. 1079–1092.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Schar, P., Fasi, M., and Jessberger, R., Smc1 coordinates DNA double-strand break repair pathways, Nucleic Acids Res., 2004, vol. 32, no. 13, pp. 3921–3929.

    Article  PubMed Central  PubMed  Google Scholar 

  92. Lee, K. and Lee, S., Saccharomyces cerevisiae sae2- and tel1-dependent single-strand dna formation at DNA break promotes microhomology-mediated end joining, Genetics, 2007, vol. 176, no. 4, pp. 2003–2014.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Hsu, D.-W., DNA double-strand break repair pathway choice in dictyostelium, J. Cell Sci., 2011, vol. 124, pp. 1655–1663.

    Article  CAS  PubMed  Google Scholar 

  94. Pierce, A., Hu, P., Han, M., et al., Ku DNA end-binding protein modulates homologous repair of doublestrand breaks in mammalian cells, Genes Dev., 2001, vol. 15, no. 24, pp. 3237–3242.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Oksenych, V., Alt, F., Kumar, V., et al., Functional redundancy between repair factor XLF and damage response mediator 53BP1 in V(D)J recombination and DNA repair, Proc. Natl. Acad. Sci. U.S.A., 2012, vol. 109, no. 7, pp. 2455–2460.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Shahi, A., Lee, J., Kang, Y., et al., Mismatch-repair protein msh6 is associated with Ku70 and regulates DNA double-strand break repair, Nucleic Acids Res., 2011, vol. 39, no. 6, pp. 2130–2143.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Zhang, Y., Rohde, L., and Wu, H., Involvement of nucleotide excision and mismatch repair mechanisms in double strand break repair, Curr. Genom., 2009, vol. 10, no. 4, pp. 250–258.

    Article  CAS  Google Scholar 

  98. Chahwan, R., van Oers, J., Avdievich, E., et al., The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination, J. Exp. Med., 2012, vol. 209, no. 4, pp. 671–678.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Yu, A. and McVey, M., Synthesis-dependent microhomology-mediated end joining accounts for multiple types of repair junctions, Nucleic Acids Res., 2010, vol. 38, no. 17, pp. 5706–5717.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Charbonnel, C., Allain, E., Gallego, M., et al., Kinetic analysis of DNA double-strand break repair pathways in Arabidopsis, DNA Rep., 2011, vol. 10, no. 6, pp. 611–619.

    Article  CAS  Google Scholar 

  101. Charbonnel, C., Allain, E., Gallego, M., et al., Kinetic analysis of DNA double-strand break repair pathways in Arabidopsis, DNA Rep., 2011, vol. 10, no. 6, pp. 611–619.

    Article  CAS  Google Scholar 

  102. Lloyd, A., Wang, D., and Timmis, J., Single molecule PCR reveals similar patterns of non-homologous DSB repair in tobacco and Arabidopsis, PLoS One, 2012, vol. 7, no. 2, p. e32255.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  103. Singh, S., Roy, S., Choudhury, S., et al., DNA repair and recombination in higher plants: insights from comparative genomics of Arabidopsis and rice, BMC Genom., 2010, vol. 11, no. 1, p. 443.

    Article  CAS  Google Scholar 

  104. Boyko, A., Zemp, F., Filkowski, J., et al., Doublestrand break repair in plants is developmentally regulated, Plant Physiol., 2006, vol. 141, no. 2, pp. 488–497.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  105. Boulton, S. and Jackson, S., Components of the Kudependent non-homologous end-joining pathway are involved in telemetric length maintenance and telomeric silencing, EMBO J., 1998, vol. 17, no. 6, pp. 1819–1828.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  106. Heacock, M., Spangler, E., Riha, K., et al., Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining, EMBO J., 2004, vol. 23, no. 11, pp. 2304–2313.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Marcand, S., Pardo, B., Gratias, A., et al., Multiple pathways inhibit NHEJ at telomeres, Genes Dev., 2008, vol. 22, no. 9, pp. 1153–1158.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  108. Rai, R., Zheng, H., He, H., et al., The function of classical and alternative non-homologous end-joining pathways in the fusion of dysfunctional telomeres, EMBO J., 2010, vol. 29, no. 15, pp. 2598–2610.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Riha, K., Watson, M., Parkey, J., et al., Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70, EMBO J., 2002, vol. 21, no. 11, pp. 2819–2826.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  110. Ting, N., Yu, Y., Pohorelic, B., et al., Human Ku70/80 interacts directly with hTR, the RNA component of human telomerase, Nucleic Acids Res., 2005, vol. 33, no. 7, pp. 2090–2098.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  111. Watson, M. and Shippen, D., Telomere rapid deletion regulates telomere length in Arabidopsis thaliana, Mol. Cell. Biol., 2007, vol. 27, no. 5, pp. 1706–1715.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  112. Scuric, Z., Chan, C., Hafer, K., et al., Ionizing radiation induces microhomology-mediated end joining in trans in yeast and mammalian cells, Radiat. Res., 2009, vol. 171, no. 4, pp. 454–463.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  113. Wang, H., Rosidi, B., Perrault, R., et al., DNA ligase III as a candidate component of backup pathways of nonhomologous end joining, Cancer Res., 2005, vol. 65, no. 10, pp. 4020–4030.

    Article  CAS  PubMed  Google Scholar 

  114. Suzuki, J., Yamaguchi, K., Kajikawa, M., et al., Genetic evidence that the non-homologous end-joining repair pathway is involved in line retrotransposition, PLoS Genet., 2009, vol. 5, no. 4, p. e1000461.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  115. Kwon, T., Huq, E., and Herrin, D., Microhomologymediated and nonhomologous repair of a doublestrand break in the chloroplast genome of Arabidopsis, Proc. Natl. Acad. Sci. U.S.A., 2010, vol. 107, no. 31, pp. 13954–13959.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  116. Mahaney, B., Meek, K., and Lees-Miller, S., Repair of ionizing radiation-induced DNA double strand breaks by non-homologous end-joining, Biochem. J., 2009, vol. 417, no. 3, pp. 639–650.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cell Biology and Genetic Engineering, National Academy of Sciences of Ukraine, ul. Akademika Zabolotnogo 148, Kyiv, 03680, Ukraine

    S. V. Litvinov

Authors
  1. S. V. Litvinov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. V. Litvinov.

Additional information

Original Russian Text © S.V. Litvinov, 2014, published in Tsitologiya i Genetika, 2014, Vol. 48, No. 3, pp. 64–77.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Litvinov, S.V. Main repair pathways of double-strand breaks in the genomic DNA and interactions between them. Cytol. Genet. 48, 189–202 (2014). https://doi.org/10.3103/S0095452714030062

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0095452714030062

Keywords

Search

Navigation