Skip to main content
SpringerLink
Log in

Dynamics of Double-Strand Breaks: Implications for the Formation of Chromosome Translocations

  • Chapter
  • First Online:
Chromosome Translocation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1044))

Abstract

Illegitimate joining of chromosome breaks can lead to the formation of chromosome translocations, a catastrophic type of genome rearrangements that often plays key roles in tumorigenesis. Emerging evidence suggests that the mobility of broken DNA loci can be an important determinant in partner search and clustering of individual breaks, events that can influence translocation frequency. We summarize here the recent literature on the mechanisms that regulate chromatin movement, focusing on studies exploring the motion properties of double-strand breaks in the context of chromatin, the functional consequences for DNA repair, and the formation of chromosome fusions.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Boveri T (2008) Concerning the origin of malignant tumours by Theodor Boveri. Trans Annot Henry Harris J Cell Sci 121(Suppl 1):1–84. https://doi.org/10.1242/jcs.025742

    Article  Google Scholar 

  2. Mitelman F, Johansson B, Mertens F (2007) The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer 7(4):233–245. https://doi.org/10.1038/nrc2091

    Article  PubMed  CAS  Google Scholar 

  3. Roukos V, Misteli T (2014) The biogenesis of chromosome translocations. Nat Cell Biol 16(4):293–300. https://doi.org/10.1038/ncb2941

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Rowley JD (1973) Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243(5405):290–293

    Article  PubMed  CAS  Google Scholar 

  5. Mertens F, Johansson B, Fioretos T, Mitelman F (2015) The emerging complexity of gene fusions in cancer. Nat Rev Cancer 15(6):371–381. https://doi.org/10.1038/nrc3947

    Article  PubMed  CAS  Google Scholar 

  6. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science (New York NY) 310(5748):644–648. https://doi.org/10.1126/science.1117679

    Article  CAS  Google Scholar 

  7. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144(1):27–40. https://doi.org/10.1016/j.cell.2010.11.055

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Alt FW, Zhang Y, Meng FL, Guo C, Schwer B (2013) Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell 152(3):417–429. https://doi.org/10.1016/j.cell.2013.01.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Campos EI, Reinberg D (2009) Histones: annotating chromatin. Annu Rev Genet 43:559–599. https://doi.org/10.1146/annurev.genet.032608.103928

    Article  PubMed  CAS  Google Scholar 

  10. Misteli T (2013) The cell biology of genomes: bringing the double helix to life. Cell 152(6):1209–1212. https://doi.org/10.1016/j.cell.2013.02.048

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Marshall WF, Straight A, Marko JF, Swedlow J, Dernburg A, Belmont A, Murray AW, Agard DA, Sedat JW (1997) Interphase chromosomes undergo constrained diffusional motion in living cells. Curr Biol CB 7(12):930–939

    Article  PubMed  CAS  Google Scholar 

  12. Michaelis C, Ciosk R, Nasmyth K (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91(1):35–45

    Article  PubMed  CAS  Google Scholar 

  13. Roukos V, Burgess RC, Misteli T (2014) Generation of cell-based systems to visualize chromosome damage and translocations in living cells. Nat Protoc 9(10):2476–2492. https://doi.org/10.1038/nprot.2014.167

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Robinett CC, Straight A, Li G, Willhelm C, Sudlow G, Murray A, Belmont AS (1996) In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition. J Cell Biol 135(6 Pt 2):1685–1700

    Article  PubMed  CAS  Google Scholar 

  15. Chubb JR, Boyle S, Perry P, Bickmore WA (2002) Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol CB 12(6):439–445

    Article  PubMed  CAS  Google Scholar 

  16. Vazquez J, Belmont AS, Sedat JW (2001) Multiple regimes of constrained chromosome motion are regulated in the interphase Drosophila nucleus. Curr Biol CB 11(16):1227–1239

    Article  PubMed  CAS  Google Scholar 

  17. Heun P, Laroche T, Shimada K, Furrer P, Gasser SM (2001) Chromosome dynamics in the yeast interphase nucleus. Science (New York, NY) 294(5549):2181–2186. https://doi.org/10.1126/science.1065366

    Article  CAS  Google Scholar 

  18. Dion V, Kalck V, Seeber A, Schleker T, Gasser SM (2013) Cohesin and the nucleolus constrain the mobility of spontaneous repair foci. EMBO Rep 14(11):984–991. https://doi.org/10.1038/embor.2013.142

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Roukos V, Voss TC, Schmidt CK, Lee S, Wangsa D, Misteli T (2013) Spatial dynamics of chromosome translocations in living cells. Science (New York, NY) 341(6146):660–664. https://doi.org/10.1126/science.1237150

    Article  CAS  Google Scholar 

  20. Weber SC, Spakowitz AJ, Theriot JA (2012) Nonthermal ATP-dependent fluctuations contribute to the in vivo motion of chromosomal loci. Proc Natl Acad Sci U S A 109(19):7338–7343. https://doi.org/10.1073/pnas.1119505109

    Article  PubMed  PubMed Central  Google Scholar 

  21. Neumann FR, Dion V, Gehlen LR, Tsai-Pflugfelder M, Schmid R, Taddei A, Gasser SM (2012) Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes Dev 26(4):369–383. https://doi.org/10.1101/gad.176156.111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Wiesmeijer K, Krouwels IM, Tanke HJ, Dirks RW (2008) Chromatin movement visualized with photoactivable GFP-labeled histone H4. Differentiation 76(1):83–90. https://doi.org/10.1111/j.1432-0436.2007.00234.x

    Article  PubMed  CAS  Google Scholar 

  23. Walter J, Schermelleh L, Cremer M, Tashiro S, Cremer T (2003) Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages. J Cell Biol 160(5):685–697. https://doi.org/10.1083/jcb.200211103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Thomson I, Gilchrist S, Bickmore WA, Chubb JR (2004) The radial positioning of chromatin is not inherited through mitosis but is established de novo in early G1. Curr Biol CB 14(2):166–172

    Article  PubMed  CAS  Google Scholar 

  25. Krawczyk PM, Borovski T, Stap J, Cijsouw A, Ten Cate R, Medema JP, Kanaar R, Franken NA, Aten JA (2012) Chromatin mobility is increased at sites of DNA double-strand breaks. J Cell Sci. https://doi.org/10.1242/jcs.089847

  26. Pliss A, Malyavantham K, Bhattacharya S, Zeitz M, Berezney R (2009) Chromatin dynamics is correlated with replication timing. Chromosoma 118(4):459–470. https://doi.org/10.1007/s00412-009-0208-6

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chuang CH, Carpenter AE, Fuchsova B, Johnson T, de Lanerolle P, Belmont AS (2006) Long-range directional movement of an interphase chromosome site. Curr Biol CB 16(8):825–831. https://doi.org/10.1016/j.cub.2006.03.059

    Article  PubMed  CAS  Google Scholar 

  28. Hediger F, Neumann FR, Van Houwe G, Dubrana K, Gasser SM (2002) Live imaging of telomeres: yKu and sir proteins define redundant telomere-anchoring pathways in yeast. Curr Biol CB 12 (24):2076–2089.

    Article  PubMed  CAS  Google Scholar 

  29. Therizols P, Illingworth RS, Courilleau C, Boyle S, Wood AJ, Bickmore WA (2014) Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells. Science (New York, NY) 346(6214):1238–1242. https://doi.org/10.1126/science.1259587

    Article  CAS  Google Scholar 

  30. Spichal M, Brion A, Herbert S, Cournac A, Marbouty M, Zimmer C, Koszul R, Fabre E (2016) Evidence for a dual role of actin in regulating chromosome organization and dynamics in yeast. J Cell Sci 129(4):681–692. https://doi.org/10.1242/jcs.175745

    Article  PubMed  CAS  Google Scholar 

  31. Zimmer C, Fabre E (2011) Principles of chromosomal organization: lessons from yeast. J Cell Biol 192(5):723–733. https://doi.org/10.1083/jcb.201010058

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Taddei A, Schober H, Gasser SM (2010) The budding yeast nucleus. Cold Spring Harb Perspect Biol 2(8):a000612. https://doi.org/10.1101/cshperspect.a000612

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Lukas J, Lukas C, Bartek J (2011) More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol 13(10):1161–1169. https://doi.org/10.1038/ncb2344

    Article  PubMed  CAS  Google Scholar 

  34. Aten JA, Stap J, Krawczyk PM, van Oven CH, Hoebe RA, Essers J, Kanaar R (2004) Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains. Science (New York, NY) 303(5654):92–95. https://doi.org/10.1126/science.1088845

    Article  CAS  Google Scholar 

  35. Jakob B, Splinter J, Durante M, Taucher-Scholz G (2009) Live cell microscopy analysis of radiation-induced DNA double-strand break motion. Proc Natl Acad Sci U S A 106(9):3172–3177. https://doi.org/10.1073/pnas.0810987106

    Article  PubMed  PubMed Central  Google Scholar 

  36. Nelms BE, Maser RS, MacKay JF, Lagally MG, Petrini JH (1998) In situ visualization of DNA double-strand break repair in human fibroblasts. Science (New York, NY) 280(5363):590–592

    Article  CAS  Google Scholar 

  37. Dion V, Kalck V, Horigome C, Towbin BD, Gasser SM (2012) Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nat Cell Biol 14(5):502–509. https://doi.org/10.1038/ncb2465

    Article  PubMed  CAS  Google Scholar 

  38. Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, Ried T, Danuser G, Misteli T (2007) Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol 9(6):675–682. https://doi.org/10.1038/ncb1591

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Kato L, Begum NA, Burroughs AM, Doi T, Kawai J, Daub CO, Kawaguchi T, Matsuda F, Hayashizaki Y, Honjo T (2012) Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes. Proc Natl Acad Sci U S A 109(7):2479–2484. https://doi.org/10.1073/pnas.1120791109

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lobachev K, Vitriol E, Stemple J, Resnick MA, Bloom K (2004) Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex. Curr Biol CB 14(23):2107–2112. https://doi.org/10.1016/j.cub.2004.11.051

    Article  PubMed  CAS  Google Scholar 

  41. Kruhlak MJ, Celeste A, Dellaire G, Fernandez-Capetillo O, Muller WG, McNally JG, Bazett-Jones DP, Nussenzweig A (2006) Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks. J Cell Biol 172(6):823–834. https://doi.org/10.1083/jcb.200510015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Mine-Hattab J, Rothstein R (2012) Increased chromosome mobility facilitates homology search during recombination. Nat Cell Biol 14(5):510–517. https://doi.org/10.1038/ncb2472

    Article  PubMed  CAS  Google Scholar 

  43. Saad H, Gallardo F, Dalvai M, Tanguy-le-Gac N, Lane D, Bystricky K (2014) DNA dynamics during early double-strand break processing revealed by non-intrusive imaging of living cells. PLoS Genet 10(3):e1004187. https://doi.org/10.1371/journal.pgen.1004187

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Strecker J, Gupta GD, Zhang W, Bashkurov M, Landry MC, Pelletier L, Durocher D (2016) DNA damage signalling targets the kinetochore to promote chromatin mobility. Nat Cell Biol 18(3):281–290. https://doi.org/10.1038/ncb3308

    Article  PubMed  CAS  Google Scholar 

  45. Cho NW, Dilley RL, Lampson MA, Greenberg RA (2014) Interchromosomal homology searches drive directional ALT telomere movement and synapsis. Cell 159(1):108–121. https://doi.org/10.1016/j.cell.2014.08.030

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Gandhi M, Evdokimova VN, TC K, Nikiforova MN, Kelly LM, Stringer JR, Bakkenist CJ, Nikiforov YE (2012) 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 109(24):9454–9459. https://doi.org/10.1073/pnas.1205759109

    Article  PubMed  PubMed Central  Google Scholar 

  47. Chiolo I, Minoda A, Colmenares SU, Polyzos A, Costes SV, Karpen GH (2011) Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell 144(5):732–744. https://doi.org/10.1016/j.cell.2011.02.012

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Jakob B, Splinter J, Conrad S, Voss KO, Zink D, Durante M, Lobrich M, Taucher-Scholz G (2011) DNA double-strand breaks in heterochromatin elicit fast repair protein recruitment, histone H2AX phosphorylation and relocation to euchromatin. Nucleic Acids Res 39(15):6489–6499. https://doi.org/10.1093/nar/gkr230

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Tsouroula K, Furst A, Rogier M, Heyer V, Maglott-Roth A, Ferrand A, Reina-San-Martin B, Soutoglou E (2016) Temporal and spatial uncoupling of DNA double strand break repair pathways within mammalian heterochromatin. Mol Cell 63(2):293–305. https://doi.org/10.1016/j.molcel.2016.06.002

    Article  PubMed  CAS  Google Scholar 

  50. Torres-Rosell J, Sunjevaric I, De Piccoli G, Sacher M, Eckert-Boulet N, Reid R, Jentsch S, Rothstein R, Aragon L, Lisby M (2007) The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol 9(8):923–931. https://doi.org/10.1038/ncb1619

    Article  PubMed  CAS  Google Scholar 

  51. Kim JA, Kruhlak M, Dotiwala F, Nussenzweig A, Haber JE (2007) Heterochromatin is refractory to gamma-H2AX modification in yeast and mammals. J Cell Biol 178(2):209–218. https://doi.org/10.1083/jcb.200612031

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Lemaitre C, Grabarz A, Tsouroula K, Andronov L, Furst A, Pankotai T, Heyer V, Rogier M, Attwood KM, Kessler P, Dellaire G, Klaholz B, Reina-San-Martin B, Soutoglou E (2014) Nuclear position dictates DNA repair pathway choice. Genes Dev 28(22):2450–2463. https://doi.org/10.1101/gad.248369.114

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Misteli T, Soutoglou E (2009) The emerging role of nuclear architecture in DNA repair and genome maintenance. Nat Rev Mol Cell Biol 10(4):243–254. https://doi.org/10.1038/nrm2651

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Dimitrova N, Chen YC, Spector DL, de Lange T (2008) 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature 456(7221):524–528. https://doi.org/10.1038/nature07433

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Seeber A, Dion V, Gasser SM (2013) Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global chromatin mobility in response to DNA damage. Genes Dev 27(18):1999–2008. https://doi.org/10.1101/gad.222992.113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Dundr M, Ospina JK, Sung MH, John S, Upender M, Ried T, Hager GL, Matera AG (2007) Actin-dependent intranuclear repositioning of an active gene locus in vivo. J Cell Biol 179(6):1095–1103. https://doi.org/10.1083/jcb.200710058

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Lottersberger F, Karssemeijer RA, Dimitrova N, de Lange T (2015) 53BP1 and the LINC complex promote microtubule-dependent DSB mobility and DNA repair. Cell 163(4):880–893. https://doi.org/10.1016/j.cell.2015.09.057

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Aymard F, Aguirrebengoa M, Guillou E, Javierre BM, Bugler B, Arnould C, Rocher V, Iacovoni JS, Biernacka A, Skrzypczak M, Ginalski K, Rowicka M, Fraser P, Legube G (2017) Genome-wide mapping of long-range contacts unveils clustering of DNA double-strand breaks at damaged active genes. Nat Struct Mol Biol 24(4):353–361. https://doi.org/10.1038/nsmb.3387

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Lisby M, Mortensen UH, Rothstein R (2003) Colocalization of multiple DNA double-strand breaks at a single Rad52 repair Centre. Nat Cell Biol 5(6):572–577. https://doi.org/10.1038/ncb997

    Article  PubMed  CAS  Google Scholar 

  60. Caron P, Choudjaye J, Clouaire T, Bugler B, Daburon V, Aguirrebengoa M, Mangeat T, Iacovoni JS, Alvarez-Quilon A, Cortes-Ledesma F, Legube G (2015) Non-redundant functions of ATM and DNA-PKcs in response to DNA double-strand breaks. Cell Rep 13(8):1598–1609. https://doi.org/10.1016/j.celrep.2015.10.024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Forget AL, Kowalczykowski SC (2012) Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search. Nature 482(7385):423–427. https://doi.org/10.1038/nature10782

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Ragunathan K, Liu C, Ha T (2012) RecA filament sliding on DNA facilitates homology search. eLife 1:e00067. https://doi.org/10.7554/eLife.00067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Renkawitz J, Lademann CA, Kalocsay M, Jentsch S (2013) Monitoring homology search during DNA double-strand break repair in vivo. Mol Cell 50(2):261–272. https://doi.org/10.1016/j.molcel.2013.02.020

    Article  PubMed  CAS  Google Scholar 

  64. Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, Fraser P (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36(10):1065–1071. https://doi.org/10.1038/ng1423

    Article  PubMed  CAS  Google Scholar 

  65. Osborne CS, Chakalova L, Mitchell JA, Horton A, Wood AL, Bolland DJ, Corcoran AE, Fraser P (2007) Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol 5(8):e192. https://doi.org/10.1371/journal.pbio.0050192

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho YJ, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M, Alt FW (2011) Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147(1):107–119. https://doi.org/10.1016/j.cell.2011.07.049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A, Nakahashi H, Di Virgilio M, Bothmer A, Nussenzweig A, Robbiani DF, Casellas R, Nussenzweig MC (2011) Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147(1):95–106. https://doi.org/10.1016/j.cell.2011.07.048

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Barlow JH, Faryabi RB, Callen E, Wong N, Malhowski A, Chen HT, Gutierrez-Cruz G, Sun HW, McKinnon P, Wright G, Casellas R, Robbiani DF, Staudt L, Fernandez-Capetillo O, Nussenzweig A (2013) Identification of early replicating fragile sites that contribute to genome instability. Cell 152(3):620–632. https://doi.org/10.1016/j.cell.2013.01.006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Lin C, Yang L, Tanasa B, Hutt K, Ju BG, Ohgi K, Zhang J, Rose DW, Fu XD, Glass CK, Rosenfeld MG (2009) Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell 139(6):1069–1083. https://doi.org/10.1016/j.cell.2009.11.030

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Mathas S, Kreher S, Meaburn KJ, Johrens K, Lamprecht B, Assaf C, Sterry W, Kadin ME, Daibata M, Joos S, Hummel M, Stein H, Janz M, Anagnostopoulos I, Schrock E, Misteli T, Dorken B (2009) Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma. Proc Natl Acad Sci U S A 106(14):5831–5836. https://doi.org/10.1073/pnas.0900912106

    Article  PubMed  PubMed Central  Google Scholar 

  71. Roukos V, Mathas S (2015) The origins of ALK translocations. Front Biosci 7:260–268

    Article  Google Scholar 

  72. Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li GW, Park J, Blackburn EH, Weissman JS, Qi LS, Huang B (2013) Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155(7):1479–1491. https://doi.org/10.1016/j.cell.2013.12.001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Ma H, Tu LC, Naseri A, Huisman M, Zhang S, Grunwald D, Pederson T (2016) Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow. Nat Biotechnol 34(5):528–530. https://doi.org/10.1038/nbt.3526

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Canela A, Sridharan S, Sciascia N, Tubbs A, Meltzer P, Sleckman BP, Nussenzweig A (2016) DNA breaks and end resection measured genome-wide by end sequencing. Mol Cell 63(5):898–911. https://doi.org/10.1016/j.molcel.2016.06.034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Crosetto N, Mitra A, Silva MJ, Bienko M, Dojer N, Wang Q, Karaca E, Chiarle R, Skrzypczak M, Ginalski K, Pasero P, Rowicka M, Dikic I (2013) Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. Nat Methods 10(4):361–365. https://doi.org/10.1038/nmeth.2408

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Tsai SQ, Zheng Z, Nguyen NT, Liebers M, Topkar VV, Thapar V, Wyvekens N, Khayter C, Iafrate AJ, Le LP, Aryee MJ, Joung JK (2015) GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33(2):187–197. https://doi.org/10.1038/nbt.3117

    Article  PubMed  CAS  Google Scholar 

  77. Hu J, Meyers RM, Dong J, Panchakshari RA, Alt FW, Frock RL (2016) Detecting DNA double-stranded breaks in mammalian genomes by linear amplification-mediated high-throughput genome-wide translocation sequencing. Nat Protoc 11(5):853–871. https://doi.org/10.1038/nprot.2016.043

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

We would like to apologize to colleagues whose work could not be cited due to space limitations. We would like to thank Dr. Karen Meaburn for critical reading of the manuscript. This work is supported by the “DFG Major Research Instrumentation Programme” (INST 247/845-1 FUGG).

Author information

Author notes

  1. Authors Henrike Johanna Gothe and Vera Minneker have equally contributed to this chapter.

Authors and Affiliations

  1. Institute of Molecular Biology, Mainz, Germany

    Henrike Johanna Gothe, Vera Minneker & Vassilis Roukos

Authors
  1. Henrike Johanna Gothe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vera Minneker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vassilis Roukos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vassilis Roukos .

Editor information

Editors and Affiliations

  1. National Institute of Biological Sciences, Beijing, China

    Yu Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gothe, H.J., Minneker, V., Roukos, V. (2018). Dynamics of Double-Strand Breaks: Implications for the Formation of Chromosome Translocations. In: Zhang, Y. (eds) Chromosome Translocation. Advances in Experimental Medicine and Biology, vol 1044. Springer, Singapore. https://doi.org/10.1007/978-981-13-0593-1_3

Download citation

Publish with us

Policies and ethics

Search

Navigation