Current Genetics

, Volume 65, Issue 1, pp 1–9 | Cite as

Chromatin mobility upon DNA damage: state of the art and remaining questions

  • Christophe ZimmerEmail author
  • Emmanuelle FabreEmail author


Chromosome organization and chromatin mobility are central to DNA metabolism. In particular, it has been recently shown by several labs that double strand breaks (DSBs) in yeast induce a change in chromatin mobility at the site of the damage. Intriguingly, DSB also induces a global mobility of the genome, at others, potentially undamaged positions. How mobility is regulated and what are the functional outcomes of these global changes in chromatin dynamics are, however, not yet fully understood. We present the current state of knowledge in light of the recent literature and discuss some perspectives opened by these discoveries towards genome stability.


Chromatin Double strand breaks Mobility Polymer physics Yeast 



This review is dedicated to Cécile Fabre Martial. We thank Karine Dubrana, Judith Miné-Hattab, Jean-Marc Victor for constructive comments about our manuscript, Etienne Almayrac and Fabiola Garcia Fernandez for their contribution to the figures and members of the consortium GDR ADN (Architecture du Noyau) for lively discussions. C.Z. acknowledges funding by Institut Pasteur, Institut National du Cancer (INCa 2015-135), Fondation pour la Recherche Médicale (Equipe FRM DEQ20150331762). E.F. acknowledges support from Agence Nationale de la Recherche (ANR-13-BSV8-0013-01), IDEX SLI (DXCAIUHSLI-EF14), Labex Who am I (ANR-11-LABX-0071, Idex ANR-11-IDEX-0005-02), Cancéropôle Ile de France (ORFOCRISE PME-2015) and Fondation pour la Recherche Médicale (ING20160435205).


  1. Albert B, Léger-Silvestre I, Normand C, Gadal O (2012) Nuclear organization and chromatin dynamics in yeast: biophysical models or biologically driven interactions? BBA Gene Regulat Mech.
  2. Amitai A, Seeber A, Gasser SM, Holcman D (2017) Visualization of chromatin decompaction and break site extrusion as predicted by statistical polymer modeling of single-locus trajectories. Cell Rep 18:1200–1214. CrossRefPubMedGoogle Scholar
  3. Arbona J-M, Herbert S, Fabre E, Zimmer C (2017) Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations. Genome Biol 18:81. CrossRefPubMedCentralPubMedGoogle Scholar
  4. Backlund MP, Joyner R, Weis K, Moerner WE (2014) Correlations of three-dimensional motion of chromosomal loci in yeast revealed by the double-helix point spread function microscope. Mol Biol Cell 25:3619–3629. CrossRefPubMedCentralPubMedGoogle Scholar
  5. Barlow JH, Lisby M, Rothstein R (2008) Differential regulation of the cellular response to DNA double-strand breaks in G1. Mol Cell 30:73–85. CrossRefPubMedCentralPubMedGoogle Scholar
  6. Belmont AS (2001) Visualizing chromosome dynamics with GFP. Trends Cell Biol 11:250–257CrossRefPubMedGoogle Scholar
  7. Bonilla CY, Melo JA, Toczyski DP (2008) Colocalization of sensors is sufficient to activate the DNA damage checkpoint in the absence of damage. Mol Cell 30:267–276. CrossRefPubMedCentralPubMedGoogle Scholar
  8. Bronshtein I, Kepten E, Kanter I et al (2015) Loss of lamin A function increases chromatin dynamics in the nuclear interior. Nat Commun 6:1–9. CrossRefGoogle Scholar
  9. Bystricky K (2015) Chromosome dynamics and folding in eukaryotes: insights from live cell microscopy. FEBS Lett 589:3014–3022. CrossRefPubMedGoogle Scholar
  10. Cabal GG, Genovesio A, Rodriguez-Navarro S et al (2006) SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope. Nature 441:770–773. CrossRefGoogle Scholar
  11. Cho NW, Dilley RL, Lampson MA, Greenberg RA (2014) Interchromosomal homology searches drive directional ALT telomere movement and synapsis. Cell 159:108–121. CrossRefPubMedCentralPubMedGoogle Scholar
  12. Chubb JR, Boyle S, Perry P, Bickmore WA (2002) Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol 12:439–445CrossRefPubMedGoogle Scholar
  13. Chung DKC, Chan JNY, Strecker J et al (2015) Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process. Nat Commun 6:1–13. CrossRefGoogle Scholar
  14. Cournac A, Marie-Nelly H, Marbouty M et al (2012) Normalization of a chromosomal contact map. BMC Genom 13:436. CrossRefGoogle Scholar
  15. Dion V, Kalck V, Horigome C et al (2012) Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nat Cell Biol 14:502–509. CrossRefPubMedGoogle Scholar
  16. Duan Z, Andronescu M, Schutz K et al (2010) A three-dimensional model of the yeast genome. Nature. CrossRefPubMedPubMedCentralGoogle Scholar
  17. Ehrenfeld GM, Shipley JB, Heimbrook DC et al (1987) Copper-dependent cleavage of DNA by bleomycin. Biochemistry 26:931–942CrossRefPubMedGoogle Scholar
  18. Faller R, Müller-Plathe F (2001) Chain stiffness intensifies the reptation characteristics of polymer dynamics in the melt. Chemphyschem 2:180–184CrossRefPubMedGoogle Scholar
  19. Finn K, Lowndes NF, Grenon M (2011) Eukaryotic DNA damage checkpoint activation in response to double-strand breaks. Cell Mol Life Sci 69:1447–1473. CrossRefPubMedGoogle Scholar
  20. George AA, Walworth NC (2016) Microtubule dynamics decoded by the epigenetic state of centromeric chromatin. Curr Genet 62:691–695. CrossRefPubMedGoogle Scholar
  21. Gibb B, Ye LF, Kwon Y et al (2014) Protein dynamics during presynaptic-complex assembly on individual single-stranded DNA molecules. Nat Struct Mol Biol 21:893–900. CrossRefPubMedCentralPubMedGoogle Scholar
  22. Grenon M, Costelloe T, Jimeno S et al (2007) Docking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain. Yeast 24:105–119. CrossRefPubMedGoogle Scholar
  23. Hajjoul H, Mathon J, Ranchon H et al (2013) High-throughput chromatin motion tracking in living yeast reveals the flexibility of the fiber throughout the genome. Genome Res 23:1829–1838. CrossRefPubMedCentralPubMedGoogle Scholar
  24. Hammet A, Magill C, Heierhorst J, Jackson SP (2007) Rad9 BRCT domain interaction with phosphorylated H2AX regulates the G1 checkpoint in budding yeast. EMBO Rep 8:851–857. CrossRefPubMedCentralPubMedGoogle Scholar
  25. Hauer MH, Seeber A, Singh V et al (2017) Histone degradation in response to DNA damage enhances chromatin dynamics and recombination rates. Nat Struct Mol Biol 1–13.
  26. Herbert S, Brion A, Arbona J-M et al (2017) Chromatin stiffening underlies enhanced locus mobility after DNA damage in budding yeast. EMBO J 36:2595–2608. CrossRefPubMedCentralPubMedGoogle Scholar
  27. Heun P (2001) Chromosome dynamics in the yeast interphase nucleus. Science 294:2181–2186. CrossRefPubMedGoogle Scholar
  28. Horigome C, Oma Y, Konishi T et al (2014) SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. Mol Cell 55:626–639. CrossRefPubMedGoogle Scholar
  29. Jin QW, Fuchs J, Loidl J (2000) Centromere clustering is a major determinant of yeast interphase nuclear organization. J Cell Sci 113(Pt 11):1903–1912PubMedGoogle Scholar
  30. Lawrimore J, Barry TM, Barry RM et al (2017) Microtubule dynamics drive enhanced chromatin motion and mobilize telomeres in response to DNA damage. Mol Biol Cell 28:1701–1711. CrossRefPubMedCentralPubMedGoogle Scholar
  31. Lee C-S, Lee K, Legube G, Haber JE (2014) SI Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break. Nat Struct Mol Biol 21:103–109. CrossRefPubMedGoogle Scholar
  32. Lottersberger F, Karssemeijer RA, Dimitrova N, de Lange T (2015) 53BP1 and the LINC complex promote microtubule-dependent DSB mobility and DNA repair. Cell 163:880–893. CrossRefPubMedCentralPubMedGoogle Scholar
  33. Marshall WF, Straight A, Marko JF et al (1997) Interphase chromosomes undergo constrained diffusional motion in living cells. Curr Biol 7:930–939CrossRefPubMedGoogle Scholar
  34. Martin SG, Laroche T, Suka N et al (1999) Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell 97:621–633CrossRefPubMedGoogle Scholar
  35. Miné-Hattab J, Rothstein R (2012) Increased chromosome mobility facilitates homology search during recombination. Nat Cell Biol. CrossRefPubMedGoogle Scholar
  36. Miné-Hattab J, Recamier V, Izeddin I, Rothstein R, Darzacq X (2017) Multi-scale tracking reveals scale-dependent chromatin dynamics after DNA damage. Mol Biol Cell 28:3323–3332CrossRefPubMedCentralGoogle Scholar
  37. Nagai S, Dubrana K, Tsai-Pflugfelder M et al (2008) Functional targeting of DNA damage to a Nuclear pore-associated SUMO-dependent ubiquitin ligase. Science 322:597. CrossRefPubMedCentralPubMedGoogle Scholar
  38. Neumann FR, Dion V, Gehlen LR et al (2012) Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes Dev 26:369–383. CrossRefPubMedCentralPubMedGoogle Scholar
  39. Palou R, Palou G, Quintana DG (2016) A role for the spindle assembly checkpoint in the DNA damage response. Curr Genet 63:275–280. CrossRefPubMedCentralPubMedGoogle Scholar
  40. Saad H, Gallardo F, Dalvai M et al (2014) DNA dynamics during early double-strand break processing revealed by non-intrusive imaging of living cells. PLoS Genet 10:e1004187–e1004111. CrossRefPubMedCentralPubMedGoogle Scholar
  41. Schober H, Kalck V, Vega-Palas MA et al (2008) Controlled exchange of chromosomal arms reveals principles driving telomere interactions in yeast. Genome Res 18:261–271. CrossRefPubMedCentralPubMedGoogle Scholar
  42. 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 27:1999–2008. CrossRefPubMedCentralPubMedGoogle Scholar
  43. Shroff R, Arbel-Eden A, Pilch D et al (2004) Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol 14:1703–1711. CrossRefPubMedCentralPubMedGoogle Scholar
  44. Spichal M, Fabre E (2017) The emerging role of the cytoskeleton in chromosome dynamics. Front Genet 8:60. CrossRefPubMedCentralPubMedGoogle Scholar
  45. Spichal M, Brion A, Herbert S et al (2016) Evidence for a dual role of actin in regulating chromosome organization and dynamics in yeast. J Cell Sci 129:681–692. CrossRefPubMedGoogle Scholar
  46. Steighner RJ, Povirk LF (1990) Bleomycin-induced DNA lesions at mutational hot spots: implications for the mechanism of double-strand cleavage. Proc Natl Acad Sci USA 87:8350–8354CrossRefPubMedGoogle Scholar
  47. Steinhauser MO, Schneider J, Blumen A (2009) Simulating dynamic crossover behavior of semiflexible linear polymers in solution and in the melt. J Chem Phys 130:164902–164909. CrossRefPubMedGoogle Scholar
  48. Strecker J, Gupta GD, Zhang W et al (2016) DNA damage signalling targets the kinetochore to promote chromatin mobility. Nat Cell Biol 18:281–290. CrossRefPubMedGoogle Scholar
  49. Tam ATY, Pike BL, Hammet A, Heierhorst J (2007) Telomere-related functions of yeast KU in the repair of bleomycin-induced DNA damage. Biochem Biophys Res Commun 357:800–803. CrossRefPubMedGoogle Scholar
  50. Therizols P, Fairhead C, Cabal GG et al (2006) Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region. J Cell Biol 172:189–199. CrossRefPubMedCentralPubMedGoogle Scholar
  51. Therizols P, Duong T, Dujon B et al (2010) Chromosome arm length and nuclear constraints determine the dynamic relationship of yeast subtelomeres. Proc Natl Acad Sci 107:2025–2030. CrossRefPubMedGoogle Scholar
  52. Tsukuda T, Fleming AB, Nickoloff JA, Osley MA (2005) Chromatin remodelling at a DNA double-strand break site in Saccharomyces cerevisiae. Nature 438:379–383. CrossRefPubMedCentralPubMedGoogle Scholar
  53. Uhlmann F, Lottspeich F, Nasmyth K (1999) Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature 400:37–42. CrossRefPubMedGoogle Scholar
  54. Verdaasdonk JS, Vasquez PA, Barry RM et al (2013) Centromere tethering confines chromosome domains. Mol Cell 52:819–831. CrossRefPubMedGoogle Scholar
  55. Walker JR, Corpina RA, Goldberg J (2001) Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412:607–614. CrossRefPubMedGoogle Scholar
  56. Weber SC, Spakowitz AJ, Theriot JA (2010) Bacterial chromosomal loci move subdiffusively through a viscoelastic cytoplasm. Phys Rev Lett 104:238102. CrossRefPubMedCentralPubMedGoogle Scholar
  57. Weinert TA, Hartwell LH (1993) Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics 134:63–80PubMedCentralPubMedGoogle Scholar
  58. Wong H, Marie-Nelly H, Herbert S et al (2012) A predictive computational model of the dynamic 3D interphase yeast nucleus. Curr Biol 22:1881–1890. CrossRefPubMedGoogle Scholar
  59. Zhu Z, Chung W-H, Shim EY et al (2008) Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 134:981–994. CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Unité Imagerie et ModélisationInstitut PasteurParisFrance
  2. 2.UMR 3691, CNRS; C3BI, USR 3756, IP CNRSParisFrance
  3. 3.Equipe Biologie et Dynamique des Chromosomes, Institut Universitaire d’HématologieHôpital St. LouisParisFrance
  4. 4.CNRS UMR 7212, INSERM U944, IUH, Université Paris Diderot Sorbonne Paris CitéParisFrance

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