ATM alters the otherwise robust chromatin mobility at sites of DNA double-strand breaks (DSBs) in human cells
Ionizing radiation induces DNA double strand breaks (DSBs) which can lead to the formation of chromosome rearrangements through error prone repair. In mammalian cells the positional stability of chromatin contributes to the maintenance of genome integrity. DSBs exhibit only a small, submicron scale...
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| description | Ionizing radiation induces DNA double strand breaks (DSBs) which can lead to the formation of chromosome rearrangements through error prone repair. In mammalian cells the positional stability of chromatin contributes to the maintenance of genome integrity. DSBs exhibit only a small, submicron scale diffusive mobility, but a slight increase in the mobility of chromatin domains by the induction of DSBs might influence repair fidelity and the formation of translocations. The radiation-induced local DNA decondensation in the vicinity of DSBs is one factor potentially enhancing the mobility of DSB-containing chromatin domains. Therefore in this study we focus on the influence of different chromatin modifying proteins, known to be activated by the DNA damage response, on the mobility of DSBs. IRIF (ionizing radiation induced foci) in U2OS cells stably expressing 53BP1-GFP were used as a surrogate marker of DSBs. Low angle charged particle irradiation, known to trigger a pronounced DNA decondensation, was used for the defined induction of linear tracks of IRIF. Our results show that movement of IRIF is independent of the investigated chromatin modifying proteins like ACF1 or PARP1 and PARG. Also depletion of proteins that tether DNA strands like MRE11 and cohesin did not alter IRIF dynamics significantly. Inhibition of ATM, a key component of DNA damage response signaling, resulted in a pronounced confinement of DSB mobility, which might be attributed to a diminished radiation induced decondensation. This confinement following ATM inhibition was confirmed using X-rays, proving that this effect is not restricted to densely ionizing radiation. In conclusion, repair sites of DSBs exhibit a limited mobility on a small spatial scale that is mainly unaffected by depletion of single remodeling or DNA tethering proteins. However, it relies on functional ATM kinase which is considered to influence the chromatin structure after irradiation. |
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In mammalian cells the positional stability of chromatin contributes to the maintenance of genome integrity. DSBs exhibit only a small, submicron scale diffusive mobility, but a slight increase in the mobility of chromatin domains by the induction of DSBs might influence repair fidelity and the formation of translocations. The radiation-induced local DNA decondensation in the vicinity of DSBs is one factor potentially enhancing the mobility of DSB-containing chromatin domains. Therefore in this study we focus on the influence of different chromatin modifying proteins, known to be activated by the DNA damage response, on the mobility of DSBs. IRIF (ionizing radiation induced foci) in U2OS cells stably expressing 53BP1-GFP were used as a surrogate marker of DSBs. Low angle charged particle irradiation, known to trigger a pronounced DNA decondensation, was used for the defined induction of linear tracks of IRIF. Our results show that movement of IRIF is independent of the investigated chromatin modifying proteins like ACF1 or PARP1 and PARG. Also depletion of proteins that tether DNA strands like MRE11 and cohesin did not alter IRIF dynamics significantly. Inhibition of ATM, a key component of DNA damage response signaling, resulted in a pronounced confinement of DSB mobility, which might be attributed to a diminished radiation induced decondensation. This confinement following ATM inhibition was confirmed using X-rays, proving that this effect is not restricted to densely ionizing radiation. In conclusion, repair sites of DSBs exhibit a limited mobility on a small spatial scale that is mainly unaffected by depletion of single remodeling or DNA tethering proteins. However, it relies on functional ATM kinase which is considered to influence the chromatin structure after irradiation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0092640</identifier><identifier>PMID: 24651490</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ataxia Telangiectasia Mutated Proteins - genetics ; Ataxia Telangiectasia Mutated Proteins - metabolism ; Biology and life sciences ; Cell Cycle Proteins - metabolism ; Cell Line ; Cells (Biology) ; Charged particles ; Chromatin ; Chromatin - genetics ; Chromatin - metabolism ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone - metabolism ; Chromosome rearrangements ; Chromosome translocations ; Chromosomes ; Cohesin ; Cohesins ; Confinement ; Deoxyribonucleic acid ; Depletion ; DNA ; DNA Breaks, Double-Stranded ; DNA damage ; DNA Repair ; Double-strand break repair ; Gene Expression ; Gene Knockdown Techniques ; Genes, Reporter ; Genomes ; Humans ; Inhibition ; Ionizing radiation ; Irradiation ; Kinases ; Mammalian cells ; Medicine and Health Sciences ; Mobility ; MRE11 protein ; Multiprotein Complexes - metabolism ; Poly(ADP-ribose) polymerase ; Poly(ADP-ribose) Polymerase 1 ; Poly(ADP-ribose) Polymerases - metabolism ; Proteins ; Radiation ; Radiation damage ; Radiation effects ; Repair ; Signaling ; Tethering ; Transcription Factors - metabolism ; Yeast</subject><ispartof>PloS one, 2014-03, Vol.9 (3), p.e92640-e92640</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Becker et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Becker et al 2014 Becker et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-bf28673fa7bee25331952e3884f8898f07a035d2509a92c819a2a34946d00d323</citedby><cites>FETCH-LOGICAL-c659t-bf28673fa7bee25331952e3884f8898f07a035d2509a92c819a2a34946d00d323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961414/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961414/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24651490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hancock, Ronald</contributor><creatorcontrib>Becker, Annabelle</creatorcontrib><creatorcontrib>Durante, Marco</creatorcontrib><creatorcontrib>Taucher-Scholz, Gisela</creatorcontrib><creatorcontrib>Jakob, Burkhard</creatorcontrib><title>ATM alters the otherwise robust chromatin mobility at sites of DNA double-strand breaks (DSBs) in human cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ionizing radiation induces DNA double strand breaks (DSBs) which can lead to the formation of chromosome rearrangements through error prone repair. In mammalian cells the positional stability of chromatin contributes to the maintenance of genome integrity. DSBs exhibit only a small, submicron scale diffusive mobility, but a slight increase in the mobility of chromatin domains by the induction of DSBs might influence repair fidelity and the formation of translocations. The radiation-induced local DNA decondensation in the vicinity of DSBs is one factor potentially enhancing the mobility of DSB-containing chromatin domains. Therefore in this study we focus on the influence of different chromatin modifying proteins, known to be activated by the DNA damage response, on the mobility of DSBs. IRIF (ionizing radiation induced foci) in U2OS cells stably expressing 53BP1-GFP were used as a surrogate marker of DSBs. Low angle charged particle irradiation, known to trigger a pronounced DNA decondensation, was used for the defined induction of linear tracks of IRIF. 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metabolism</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Poly(ADP-ribose) Polymerase 1</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Proteins</subject><subject>Radiation</subject><subject>Radiation damage</subject><subject>Radiation effects</subject><subject>Repair</subject><subject>Signaling</subject><subject>Tethering</subject><subject>Transcription Factors - metabolism</subject><subject>Yeast</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu1DAUjRCIloE_QGCJTVnM4HfsDdLQ8qhUYEFZWzeJM-MhiQfbAfXvcTpp1aLKlm3Z55z78CmKlwSvCCvJu50fwwDdau8Hu8JYU8nxo-KYaEaXkmL2-M75qHgW4w5jwZSUT4sjyqUgXOPjol9ffkXQJRsiSluLfF7CXxctCr4aY0L1NvgekhtQ7yvXuXSFIKHoko3It-js2xo1fqw6u4wpwNCgKlj4FdHJ2Y8P8S3KvO3Yw4Bq23XxefGkhS7aF_O-KH5--nh5-mV58f3z-en6YllLodOyaqmSJWuhrKylgjGiBbVMKd4qpVWLS8BMNFRgDZrWimigwLjmssG4YZQtitcH3X3no5k7FQ0RONOJxmVGnB8QjYed2QfXQ7gyHpy5vvBhYyAkV3fWMGUrsBJK1hAuBECFSa2V1KTJs52ivZ-jjVVvm9oOuRPdPdH7L4Pbmo3_Y5iWhBOeBU5mgeB_jzYm07s4NQwG68frvDXHiuX_WxRv_oM-XN2M2kAuwA2tz3HrSdSsealKIUsy5b16AJVHY3tXZ1u1Lt_fI_ADoQ4-xmDb2xoJNpMpb5IxkynNbMpMe3W3P7ekGxeyf9uj3TQ</recordid><startdate>20140320</startdate><enddate>20140320</enddate><creator>Becker, Annabelle</creator><creator>Durante, Marco</creator><creator>Taucher-Scholz, Gisela</creator><creator>Jakob, Burkhard</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140320</creationdate><title>ATM alters the otherwise robust chromatin mobility at sites of DNA double-strand breaks (DSBs) in human cells</title><author>Becker, Annabelle ; Durante, Marco ; Taucher-Scholz, Gisela ; Jakob, Burkhard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c659t-bf28673fa7bee25331952e3884f8898f07a035d2509a92c819a2a34946d00d323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Ataxia Telangiectasia Mutated Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Becker, Annabelle</au><au>Durante, Marco</au><au>Taucher-Scholz, Gisela</au><au>Jakob, Burkhard</au><au>Hancock, Ronald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ATM alters the otherwise robust chromatin mobility at sites of DNA double-strand breaks (DSBs) in human cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-03-20</date><risdate>2014</risdate><volume>9</volume><issue>3</issue><spage>e92640</spage><epage>e92640</epage><pages>e92640-e92640</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ionizing radiation induces DNA double strand breaks (DSBs) which can lead to the formation of chromosome rearrangements through error prone repair. In mammalian cells the positional stability of chromatin contributes to the maintenance of genome integrity. DSBs exhibit only a small, submicron scale diffusive mobility, but a slight increase in the mobility of chromatin domains by the induction of DSBs might influence repair fidelity and the formation of translocations. The radiation-induced local DNA decondensation in the vicinity of DSBs is one factor potentially enhancing the mobility of DSB-containing chromatin domains. Therefore in this study we focus on the influence of different chromatin modifying proteins, known to be activated by the DNA damage response, on the mobility of DSBs. IRIF (ionizing radiation induced foci) in U2OS cells stably expressing 53BP1-GFP were used as a surrogate marker of DSBs. Low angle charged particle irradiation, known to trigger a pronounced DNA decondensation, was used for the defined induction of linear tracks of IRIF. Our results show that movement of IRIF is independent of the investigated chromatin modifying proteins like ACF1 or PARP1 and PARG. Also depletion of proteins that tether DNA strands like MRE11 and cohesin did not alter IRIF dynamics significantly. Inhibition of ATM, a key component of DNA damage response signaling, resulted in a pronounced confinement of DSB mobility, which might be attributed to a diminished radiation induced decondensation. This confinement following ATM inhibition was confirmed using X-rays, proving that this effect is not restricted to densely ionizing radiation. In conclusion, repair sites of DSBs exhibit a limited mobility on a small spatial scale that is mainly unaffected by depletion of single remodeling or DNA tethering proteins. However, it relies on functional ATM kinase which is considered to influence the chromatin structure after irradiation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24651490</pmid><doi>10.1371/journal.pone.0092640</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Ataxia Telangiectasia Mutated Proteins - genetics Ataxia Telangiectasia Mutated Proteins - metabolism Biology and life sciences Cell Cycle Proteins - metabolism Cell Line Cells (Biology) Charged particles Chromatin Chromatin - genetics Chromatin - metabolism Chromatin Assembly and Disassembly Chromosomal Proteins, Non-Histone - metabolism Chromosome rearrangements Chromosome translocations Chromosomes Cohesin Cohesins Confinement Deoxyribonucleic acid Depletion DNA DNA Breaks, Double-Stranded DNA damage DNA Repair Double-strand break repair Gene Expression Gene Knockdown Techniques Genes, Reporter Genomes Humans Inhibition Ionizing radiation Irradiation Kinases Mammalian cells Medicine and Health Sciences Mobility MRE11 protein Multiprotein Complexes - metabolism Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase 1 Poly(ADP-ribose) Polymerases - metabolism Proteins Radiation Radiation damage Radiation effects Repair Signaling Tethering Transcription Factors - metabolism Yeast |
| title | ATM alters the otherwise robust chromatin mobility at sites of DNA double-strand breaks (DSBs) in human cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T03%3A35%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ATM%20alters%20the%20otherwise%20robust%20chromatin%20mobility%20at%20sites%20of%20DNA%20double-strand%20breaks%20(DSBs)%20in%20human%20cells&rft.jtitle=PloS%20one&rft.au=Becker,%20Annabelle&rft.date=2014-03-20&rft.volume=9&rft.issue=3&rft.spage=e92640&rft.epage=e92640&rft.pages=e92640-e92640&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0092640&rft_dat=%3Cgale_plos_%3EA478756712%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1508981907&rft_id=info:pmid/24651490&rft_galeid=A478756712&rft_doaj_id=oai_doaj_org_article_38ebae6a73d1455aab01c98691d91df2&rfr_iscdi=true |