DNA double-strand breaks (DSBs) must be rejoined properly to prevent the occurrence of serious genomic rearrangements associated with many human diseases. Non-homologous end joining (NHEJ) is a DSB repair mechanism known to protect genomic integrity that is also implicated in creating genomic translocations, inversions, deletions, and insertions. We recently investigated the impact of the pre-damage spatial proximity of DSB-bearing loci on the frequency of trans repair by NHEJ and surprisingly found no correlation between them. In this review, we consider various models that might account for these unexpected results. While DSB movement is necessary to explain our findings, many questions remain about the nature and timing of that motion.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Agmon N, Liefshitz B, Zimmer C, Fabre E, Kupiec M (2013) Effect of nuclear architecture on the efficiency of double-strand break repair. Nat Cell Biol 15(6):694–699
Aylon Y, Liefshitz B, Kupiec M (2004) The CDK regulates repair of double-strand breaks by homologous recombination during the cell cycle. EMBO J 23(24):4868–4875
Aymard F et al (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
Bordelet H, Dubrana K (2019) Keep moving and stay in a good shape to find your homologous recombination partner. Curr Genet 65(1):29–39
Caridi CP et al (2018) Nuclear F-actin and myosins drive relocalization of heterochromatic breaks. Nature 559(7712):54–60
Chiolo I et al (2011) Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell 144(5):732–744
Cho NW, Dilley RL, Lampson MA, Greenberg RA (2014) Interchromosomal homology searches drive directional ALT telomere movement and synapsis. Cell 159(1):108–121
Clouaire T et al (2018) Comprehensive mapping of histone modifications at DNA double-strand breaks deciphers repair pathway chromatin signatures. Mol Cell 72(2):250–262
Dion V, Gasser SM (2013) Chromatin movement in the maintenance of genome stability. Cell 152(6):1355–1364
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
Falk M et al (2019) Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature 570(7761):395–399
Fontana GA et al (2019) Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane. Nat Commun 10(1):2535
Gao S, Honey S, Futcher B, Grollman AP (2016) The non-homologous end-joining pathway of S. cerevisiae works effectively in G1-phase cells, and religates cognate ends correctly and non-randomly. DNA Repair (Amst) 42:1–10
Haber JE, Leung WY (1996) Lack of chromosome territoriality in yeast: promiscuous rejoining of broken chromosome ends. Proc Natl Acad Sci USA 93(24):13949–13954
Jackson SP (2001) Detecting, signalling and repairing DNA double-strand breaks. Biochem Soc Trans 29(Pt 6):655–661
Larson AG, Narlikar GJ (2018) The role of phase separation in heterochromatin formation, function and regulation. Biochemistry 57(17):2540–2548
Lee K, Zhang Y, Lee SE (2008) Saccharomyces cerevisiae ATM orthologue suppresses break-induced chromosome translocations. Nature 454(7203):543–546
Lee CS et al (2016) Chromosome position determines the success of double-strand break repair. Proc Natl Acad Sci USA 113(2):E146–E154
Lemaitre C et al (2014) Nuclear position dictates DNA repair pathway choice. Genes Dev 28(22):2450–2463
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
Lobrich M, Jeggo P (2017) A process of resection-dependent nonhomologous end joining involving the goddess Artemis. Trends Biochem Sci 42(9):690–701
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
Mine-Hattab J, Rothstein R (2012) Increased chromosome mobility facilitates homology search during recombination. Nat Cell Biol 14(5):510–517
Mine-Hattab J, Rothstein R (2013) DNA in motion during double-strand break repair. Trends Cell Biol 23(11):529–536
Mjelle R et al (2015) Cell cycle regulation of human DNA repair and chromatin remodeling genes. DNA Repair (Amst) 30:53–67
Neumann FR et al (2012) Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes Dev 26(4):369–383
Paques F, Haber JE (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63(2):349–404
Roukos V et al (2013) Spatial dynamics of chromosome translocations in living cells. Science 341(6146):660–664
Schrank BR et al (2018) Nuclear ARP2/3 drives DNA break clustering for homology-directed repair. Nature 559(7712):61–66
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
Sunder S, Wilson TE (2019) Frequency of DNA end joining in trans is not determined by the predamage spatial proximity of double-strand breaks in yeast. Proc Natl Acad Sci USA 116(19):9481–9490
Torres-Rosell J et al (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
Wang RW, Lee CS, Haber JE (2017) Position effects influencing intrachromosomal repair of a double-strand break in budding yeast. PLoS ONE 12(7):e0180994
Zimmer C, Fabre E (2019) Chromatin mobility upon DNA damage: state of the art and remaining questions. Curr Genet 65(1):1–9
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Communicated by M. Kupiec.
About this article
Cite this article
Wilson, T.E., Sunder, S. Double-strand breaks in motion: implications for chromosomal rearrangement. Curr Genet 66, 1–6 (2020). https://doi.org/10.1007/s00294-019-01015-4
- DNA repair
- Non-homologous end joining
- Homologous recombination