Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks

The Journal of Cell Biology
Michael J KruhlakAndré Nussenzweig

Abstract

The repair of DNA double-strand breaks (DSBs) is facilitated by the phosphorylation of H2AX, which organizes DNA damage signaling and chromatin remodeling complexes in the vicinity of the lesion. The disruption of DNA integrity induces an alteration of chromatin architecture that has been proposed to activate the DNA damage transducing kinase ataxia telangiectasia mutated. However, little is known about the physical properties of damaged chromatin. In this study, we use a photoactivatable version of GFP-tagged histone H2B to examine the mobility and structure of chromatin containing DSBs in living cells. We find that chromatin containing DSBs exhibits limited mobility but undergoes an energy-dependent local expansion immediately after DNA damage. The localized expansion observed in real time corresponds to a 30-40% reduction in the density of chromatin fibers in the vicinity of DSBs, as measured by energy-filtering transmission electron microscopy. The observed opening of chromatin occurs independently of H2AX and ATM. We propose that localized adenosine triphosphate-dependent decondensation of chromatin at DSBs establishes an accessible subnuclear environment that facilitates DNA damage signaling and repair.

References

Jun 30, 1997·The Journal of Cell Biology·J R AbneyB A Scalettar
Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Mar 17, 1999·Methods : a Companion to Methods in Enzymology·D P Bazett-Jones, M J Hendzel
May 13, 1999·Science·A B HoutsmullerW Vermeulen
Jun 8, 1999·Molecular Biology of the Cell·M J HendzelD P Bazett-Jones
Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Dec 2, 1999·Methods : a Companion to Methods in Enzymology·D WalkerG L Hager
Jul 13, 2000·The Journal of Cell Biology·C A SpencerD P Bazett-Jones
Dec 9, 2000·Science·H T ChenA Nussenzweig
Jan 5, 2001·Nature·J A DownsS P Jackson
Mar 23, 2002·Current Biology : CB·Jonathan R ChubbWendy A Bickmore
Apr 6, 2002·Science·Arkady CelesteAndré Nussenzweig
May 30, 2002·Proceedings of the National Academy of Sciences of the United States of America·Craig H BassingFrederick W Alt
Jun 18, 2002·Nature Cell Biology·Melpomeni PlataniJason R Swedlow
Sep 14, 2002·Science·George H Patterson, Jennifer Lippincott-Schwartz
Sep 28, 2002·Nature·Alexander W BirdMichael F Christman
Oct 10, 2002·Biochemical and Biophysical Research Communications·Joseph S SiinoNikolai V Tomilin
Nov 6, 2002·Molecular and Cellular Biology·Song Qin, Mark R Parthun
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
Feb 8, 2003·The EMBO Journal·Carlos P Rubbi, Jo Milner
Apr 12, 2003·Developmental Cell·Oscar Fernandez-CapetilloAndré Nussenzweig
Apr 22, 2003·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Ying RenDavid P Bazett-Jones
May 27, 2003·Nature Cell Biology·Michael LisbyRodney Rothstein
Jun 7, 2003·Nature Cell Biology·Arkady CelesteAndré Nussenzweig
Aug 5, 2003·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Duane R PilchWilliam M Bonner
Jan 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ali JazayeriStephen P Jackson
Apr 13, 2004·Genes & Development·Craig L Peterson, Jacques Côté
Jun 16, 2004·The Journal of Experimental Medicine·Oscar Fernandez-CapetilloAndré Nussenzweig
Jul 10, 2004·Cell·Christopher J Bakkenist, Michael B Kastan
Jul 29, 2004·DNA Repair·Oscar Fernandez-CapetilloAndré Nussenzweig
Nov 5, 2004·Nature·Yentram HuyenThanos D Halazonetis

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Citations

Jan 18, 2012·Chromosoma·Angela K DeemJessica K Tyler
Aug 4, 2007·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·William G Kelly, Rodolfo Aramayo
Sep 18, 2007·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Liudmila V SolovjevaNikolai V Tomilin
Jan 29, 2011·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Leonid A Mirny
Oct 12, 2011·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Doris M SeilerAnna A Friedl
Feb 19, 2013·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Lucie JežkováStanislav Kozubek
Mar 5, 2013·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Martin FalkStanislav Kozubek
Aug 8, 2013·DNA Repair·Anastas Gospodinov, Zdenko Herceg
Aug 21, 2013·Mutation Research·Irene ChioloSylvain V Costes
Jul 23, 2013·Trends in Cell Biology·Judith Miné-Hattab, Rodney Rothstein
Feb 16, 2013·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Veronika FoltánkováEva Bártová
Feb 16, 2011·Cell Research·Shigeki NagaiSusan M Gasser
May 28, 2013·Nature·Abderrahmane Kaidi, Stephen P Jackson
May 9, 2007·Nature Cell Biology·Evi SoutoglouTom Misteli
Dec 17, 2008·Nature Cell Biology·Yong-Chul KimMichael Bustin
Aug 23, 2011·Nature Cell Biology·Marieke H Peuscher, Jacqueline J L Jacobs
Nov 14, 2008·Nature Reviews. Cancer·William M BonnerYves Pommier
Sep 7, 2012·Nature Reviews. Cancer·Gabriele SulliFabrizio d'Adda di Fagagna
Dec 19, 2012·Nature Reviews. Genetics·Manolis Papamichos-Chronakis, Craig L Peterson
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Valérie SchreiberGilbert de Murcia
Mar 12, 2009·Nature Reviews. Molecular Cell Biology·Tom Misteli, Evi Soutoglou
Sep 17, 2009·Nature Reviews. Microbiology·Allon WeinerAbraham Minsky
Mar 7, 2013·Nature Structural & Molecular Biology·Giacomo Cavalli, Tom Misteli
May 8, 2008·Nature Structural & Molecular Biology·Jiri Lukas, Jiri Bartek
Oct 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jennifer BlickwedehlNaveen Bangia
Feb 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·B JakobG Taucher-Scholz
Jan 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·David ShechterC David Allis
Sep 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Samantha G ZeitlinDon W Cleveland
Sep 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Alexandra ZidovskaTimothy J Mitchison
May 9, 2007·The Journal of Experimental Medicine·Simone DifilippantonioAndré Nussenzweig
Feb 1, 2007·DNA and Cell Biology·Emil MladenovBoyka Anachkova
Jan 8, 2013·Briefings in Functional Genomics·Ketki KaranamGalit Lahav
Sep 6, 2008·Nucleic Acids Research·Andrea KinnerGeorge Iliakis
Jan 18, 2013·Nucleic Acids Research·Denise P MuñozSteven M Yannone
Sep 25, 2012·Nucleic Acids Research·Clemens Bönisch, Sandra B Hake
Jul 2, 2010·Cold Spring Harbor Perspectives in Biology·Tom Misteli
Mar 3, 2011·Genes & Development·Sophie E Polo, Stephen P Jackson
Dec 1, 2007·Science·Laura Trinkle-Mulcahy, Angus I Lamond

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Methods Mentioned

BETA
histone acetylation
gene array
electron microscopy
electron spectroscopic imaging
fluorescence microscopy
Fluorescence
transfections

Software Mentioned

LSM510
Digital Micrograph
MetaMorph
Medical Imaging , Processing , and Visualization ( MIPAV )
Imaris
MIPAV

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