A requirement for polymerized actin in DNA double-strand break repair
Nuclear actin is involved in several nuclear processes from chromatin remodeling to transcription. Here we examined the requirement for actin polymerization in DNA double-strand break repair. Double-strand breaks are considered the most dangerous type of DNA lesion. Double-strand break repair consis...
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| Veröffentlicht in: | Nucleus (Austin, Tex.) Tex.), 2012-07, Vol.3 (4), p.384-395 |
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| creator | Andrin, Christi McDonald, Darin Attwood, Kathleen M. Rodrigue, Amélie Ghosh, Sunita Mirzayans, Razmik Masson, Jean-Yves Dellaire, Graham Hendzel, Michael J. |
| description | Nuclear actin is involved in several nuclear processes from chromatin remodeling to transcription. Here we examined the requirement for actin polymerization in DNA double-strand break repair. Double-strand breaks are considered the most dangerous type of DNA lesion. Double-strand break repair consists of a complex set of events that are tightly regulated. Failure at any step can have catastrophic consequences such as genomic instability, oncogenesis or cell death. Many proteins involved in this repair process have been identified and their roles characterized. We discovered that some DNA double-strand break repair factors are capable of associating with polymeric actin in vitro and specifically, that purified Ku70/80 interacts with polymerized actin under these conditions. We find that the disruption of polymeric actin inhibits DNA double strand break repair both in vitro and in vivo. Introduction of nuclear targeted mutant actin that cannot polymerize, or the depolymerization of endogenous actin filaments by the addition of cytochalasin D, alters the retention of Ku80 at sites of DNA damage in live cells. Our results suggest that polymeric actin is required for proper DNA double-strand break repair and may function through the stabilization of the Ku heterodimer at the DNA damage site. |
| doi_str_mv | 10.4161/nucl.21055 |
| format | Article |
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Here we examined the requirement for actin polymerization in DNA double-strand break repair. Double-strand breaks are considered the most dangerous type of DNA lesion. Double-strand break repair consists of a complex set of events that are tightly regulated. Failure at any step can have catastrophic consequences such as genomic instability, oncogenesis or cell death. Many proteins involved in this repair process have been identified and their roles characterized. We discovered that some DNA double-strand break repair factors are capable of associating with polymeric actin in vitro and specifically, that purified Ku70/80 interacts with polymerized actin under these conditions. We find that the disruption of polymeric actin inhibits DNA double strand break repair both in vitro and in vivo. Introduction of nuclear targeted mutant actin that cannot polymerize, or the depolymerization of endogenous actin filaments by the addition of cytochalasin D, alters the retention of Ku80 at sites of DNA damage in live cells. Our results suggest that polymeric actin is required for proper DNA double-strand break repair and may function through the stabilization of the Ku heterodimer at the DNA damage site.</description><identifier>ISSN: 1949-1034</identifier><identifier>EISSN: 1949-1042</identifier><identifier>DOI: 10.4161/nucl.21055</identifier><identifier>PMID: 22688650</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Actins - chemistry ; Actins - metabolism ; Antigens, Nuclear - metabolism ; Binding ; Binding Sites ; Biology ; Bioscience ; Calcium ; Cancer ; Cell ; Cell Line, Tumor ; Cell Nucleus - metabolism ; Cycle ; DNA Breaks, Double-Stranded ; DNA Damage ; DNA Repair ; DNA-Binding Proteins - metabolism ; DSB repair ; Green Fluorescent Proteins - chemistry ; HeLa Cells ; Humans ; Ku Autoantigen ; Ku70 ; Ku80 ; Landes ; nuclear actin ; Organogenesis ; polymeric actin ; Polymerization ; Proteins</subject><ispartof>Nucleus (Austin, Tex.), 2012-07, Vol.3 (4), p.384-395</ispartof><rights>Copyright © 2012 Landes Bioscience 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-6e218f42686adba02c6269baa7888cb6c625fa3007cb3a0e352474428db1f4a03</citedby><cites>FETCH-LOGICAL-c530t-6e218f42686adba02c6269baa7888cb6c625fa3007cb3a0e352474428db1f4a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.4161/nucl.21055$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.4161/nucl.21055$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,776,780,27479,27901,27902,59116,59117</link.rule.ids><linktorsrc>$$Uhttps://www.tandfonline.com/doi/abs/10.4161/nucl.21055$$EView_record_in_Taylor_&_Francis$$FView_record_in_$$GTaylor_&_Francis</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22688650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andrin, Christi</creatorcontrib><creatorcontrib>McDonald, Darin</creatorcontrib><creatorcontrib>Attwood, Kathleen M.</creatorcontrib><creatorcontrib>Rodrigue, Amélie</creatorcontrib><creatorcontrib>Ghosh, Sunita</creatorcontrib><creatorcontrib>Mirzayans, Razmik</creatorcontrib><creatorcontrib>Masson, Jean-Yves</creatorcontrib><creatorcontrib>Dellaire, Graham</creatorcontrib><creatorcontrib>Hendzel, Michael J.</creatorcontrib><title>A requirement for polymerized actin in DNA double-strand break repair</title><title>Nucleus (Austin, Tex.)</title><addtitle>Nucleus</addtitle><description>Nuclear actin is involved in several nuclear processes from chromatin remodeling to transcription. Here we examined the requirement for actin polymerization in DNA double-strand break repair. Double-strand breaks are considered the most dangerous type of DNA lesion. Double-strand break repair consists of a complex set of events that are tightly regulated. Failure at any step can have catastrophic consequences such as genomic instability, oncogenesis or cell death. Many proteins involved in this repair process have been identified and their roles characterized. We discovered that some DNA double-strand break repair factors are capable of associating with polymeric actin in vitro and specifically, that purified Ku70/80 interacts with polymerized actin under these conditions. We find that the disruption of polymeric actin inhibits DNA double strand break repair both in vitro and in vivo. Introduction of nuclear targeted mutant actin that cannot polymerize, or the depolymerization of endogenous actin filaments by the addition of cytochalasin D, alters the retention of Ku80 at sites of DNA damage in live cells. Our results suggest that polymeric actin is required for proper DNA double-strand break repair and may function through the stabilization of the Ku heterodimer at the DNA damage site.</description><subject>Actins - chemistry</subject><subject>Actins - metabolism</subject><subject>Antigens, Nuclear - metabolism</subject><subject>Binding</subject><subject>Binding Sites</subject><subject>Biology</subject><subject>Bioscience</subject><subject>Calcium</subject><subject>Cancer</subject><subject>Cell</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - metabolism</subject><subject>Cycle</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA Damage</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>DSB repair</subject><subject>Green Fluorescent Proteins - chemistry</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Ku Autoantigen</subject><subject>Ku70</subject><subject>Ku80</subject><subject>Landes</subject><subject>nuclear actin</subject><subject>Organogenesis</subject><subject>polymeric actin</subject><subject>Polymerization</subject><subject>Proteins</subject><issn>1949-1034</issn><issn>1949-1042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVtr4zAQhcWyZVvavuwPKH5cFpxKsnzJY8imFwgptM2zGEljUNe2HMmmpL--SpNNXxYqBBrBN-eMjgj5yehEsIJdd6NuJpzRPP9GzthUTFNGBf9-rDNxSi5DeKFxCVHSnP0gp5wXVVXk9IwsZonHzWg9ttgNSe180rtm26K3b2gS0IPtkrj_rGaJcaNqMA2Dh84kyiP8jc09WH9BTmpoAl4eznOyvlk8z-_S5cPt_Xy2THWe0SEtkLOqFtG8AKOAcl3wYqoAyqqqtCriNa8ho7TUKgOKWc5FKQSvjGK1AJqdk1973d67zYhhkK0NGpsGOnRjkIxWTGSsLHfo7z2qvQvBYy17b1vw2wjJXXJyl5z8SC7CVwfdUbVojui_nCKQ74HoZDAo64K22Gk8ojs1jCOAH2ysjsLiiz5OGV-t58vF-olSxh5lb-pPO9vFH2nh1fnGyAG2jfN1TF_bILP_vOMd0IqgfQ</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Andrin, Christi</creator><creator>McDonald, Darin</creator><creator>Attwood, Kathleen M.</creator><creator>Rodrigue, Amélie</creator><creator>Ghosh, Sunita</creator><creator>Mirzayans, Razmik</creator><creator>Masson, Jean-Yves</creator><creator>Dellaire, Graham</creator><creator>Hendzel, Michael J.</creator><general>Taylor & Francis</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>7X8</scope></search><sort><creationdate>20120701</creationdate><title>A requirement for polymerized actin in DNA double-strand break repair</title><author>Andrin, Christi ; 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Here we examined the requirement for actin polymerization in DNA double-strand break repair. Double-strand breaks are considered the most dangerous type of DNA lesion. Double-strand break repair consists of a complex set of events that are tightly regulated. Failure at any step can have catastrophic consequences such as genomic instability, oncogenesis or cell death. Many proteins involved in this repair process have been identified and their roles characterized. We discovered that some DNA double-strand break repair factors are capable of associating with polymeric actin in vitro and specifically, that purified Ku70/80 interacts with polymerized actin under these conditions. We find that the disruption of polymeric actin inhibits DNA double strand break repair both in vitro and in vivo. 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| ispartof | Nucleus (Austin, Tex.), 2012-07, Vol.3 (4), p.384-395 |
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| language | eng |
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| source | Taylor & Francis Open Access |
| subjects | Actins - chemistry Actins - metabolism Antigens, Nuclear - metabolism Binding Binding Sites Biology Bioscience Calcium Cancer Cell Cell Line, Tumor Cell Nucleus - metabolism Cycle DNA Breaks, Double-Stranded DNA Damage DNA Repair DNA-Binding Proteins - metabolism DSB repair Green Fluorescent Proteins - chemistry HeLa Cells Humans Ku Autoantigen Ku70 Ku80 Landes nuclear actin Organogenesis polymeric actin Polymerization Proteins |
| title | A requirement for polymerized actin in DNA double-strand break repair |
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