Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation‐treated cockayne syndrome B cells
We have previously shown that DNA repair of oxidized bases (either purines or pyrimidines) is inefficient in cells from patients with Cockayne syndrome (cs), a rare developmental and neurological genetic disorder. Here, we show for the first time that resolution of ionizing radiation (IR)‐induced pH...
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| Veröffentlicht in: | IUBMB life 2011-04, Vol.63 (4), p.272-276 |
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| creator | Ropolo, Monica Cappelli, Enrico Foresta, Mara Poggi, Alessandro Proietti‐De‐Santis, Luca Frosina, Guido |
| description | We have previously shown that DNA repair of oxidized bases (either purines or pyrimidines) is inefficient in cells from patients with Cockayne syndrome (cs), a rare developmental and neurological genetic disorder. Here, we show for the first time that resolution of ionizing radiation (IR)‐induced pH2AX foci, an indicator of DNA double‐strand breaks, is significantly delayed in IR‐treated cells belonging to the B complementation group of cs (csb). Using alkaline single‐cell gel electrophoresis, which predominantly detects single‐strand breaks, we further demonstrate elevated DNA breakage in csb cells early after irradiation. Both the delayed resolution of pH2AX foci and the early DNA breakage of csb cells were partially complemented by expression of wild‐type CSB protein. Hence, the csb mutation impairs resolution of pH2AX foci and causes DNA fragility, broadening the spectrum of lesions whose processing is altered in this syndrome. © 2011 IUBMB IUBMB Life, 63(4): 272–276, 2011 |
| doi_str_mv | 10.1002/iub.445 |
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Here, we show for the first time that resolution of ionizing radiation (IR)‐induced pH2AX foci, an indicator of DNA double‐strand breaks, is significantly delayed in IR‐treated cells belonging to the B complementation group of cs (csb). Using alkaline single‐cell gel electrophoresis, which predominantly detects single‐strand breaks, we further demonstrate elevated DNA breakage in csb cells early after irradiation. Both the delayed resolution of pH2AX foci and the early DNA breakage of csb cells were partially complemented by expression of wild‐type CSB protein. Hence, the csb mutation impairs resolution of pH2AX foci and causes DNA fragility, broadening the spectrum of lesions whose processing is altered in this syndrome. © 2011 IUBMB IUBMB Life, 63(4): 272–276, 2011</description><identifier>ISSN: 1521-6543</identifier><identifier>EISSN: 1521-6551</identifier><identifier>DOI: 10.1002/iub.445</identifier><identifier>PMID: 21438118</identifier><identifier>CODEN: IULIF8</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., a Wiley company</publisher><subject>Cell Line ; Child, Preschool ; Cockayne syndrome ; Cockayne Syndrome - metabolism ; Cockayne Syndrome - pathology ; comet ; DNA Breaks - radiation effects ; DNA Helicases - genetics ; DNA Helicases - metabolism ; DNA Repair ; DNA Repair Enzymes - genetics ; DNA Repair Enzymes - metabolism ; Female ; Fibroblasts - metabolism ; Fibroblasts - radiation effects ; Fluorescent Antibody Technique, Direct ; H2AX ; Histones - metabolism ; Humans ; Kinetics ; Mutation ; Poly-ADP-Ribose Binding Proteins ; strand break</subject><ispartof>IUBMB life, 2011-04, Vol.63 (4), p.272-276</ispartof><rights>Copyright © 2011 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4105-dc3ca3867ee8563f481751ae625b131787f985f57542c052983641d0be89cb4d3</citedby><cites>FETCH-LOGICAL-c4105-dc3ca3867ee8563f481751ae625b131787f985f57542c052983641d0be89cb4d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fiub.445$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fiub.445$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,1432,27922,27923,45572,45573,46407,46831</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21438118$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ropolo, Monica</creatorcontrib><creatorcontrib>Cappelli, Enrico</creatorcontrib><creatorcontrib>Foresta, Mara</creatorcontrib><creatorcontrib>Poggi, Alessandro</creatorcontrib><creatorcontrib>Proietti‐De‐Santis, Luca</creatorcontrib><creatorcontrib>Frosina, Guido</creatorcontrib><title>Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation‐treated cockayne syndrome B cells</title><title>IUBMB life</title><addtitle>IUBMB Life</addtitle><description>We have previously shown that DNA repair of oxidized bases (either purines or pyrimidines) is inefficient in cells from patients with Cockayne syndrome (cs), a rare developmental and neurological genetic disorder. Here, we show for the first time that resolution of ionizing radiation (IR)‐induced pH2AX foci, an indicator of DNA double‐strand breaks, is significantly delayed in IR‐treated cells belonging to the B complementation group of cs (csb). Using alkaline single‐cell gel electrophoresis, which predominantly detects single‐strand breaks, we further demonstrate elevated DNA breakage in csb cells early after irradiation. Both the delayed resolution of pH2AX foci and the early DNA breakage of csb cells were partially complemented by expression of wild‐type CSB protein. Hence, the csb mutation impairs resolution of pH2AX foci and causes DNA fragility, broadening the spectrum of lesions whose processing is altered in this syndrome. © 2011 IUBMB IUBMB Life, 63(4): 272–276, 2011</description><subject>Cell Line</subject><subject>Child, Preschool</subject><subject>Cockayne syndrome</subject><subject>Cockayne Syndrome - metabolism</subject><subject>Cockayne Syndrome - pathology</subject><subject>comet</subject><subject>DNA Breaks - radiation effects</subject><subject>DNA Helicases - genetics</subject><subject>DNA Helicases - metabolism</subject><subject>DNA Repair</subject><subject>DNA Repair Enzymes - genetics</subject><subject>DNA Repair Enzymes - metabolism</subject><subject>Female</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - radiation effects</subject><subject>Fluorescent Antibody Technique, Direct</subject><subject>H2AX</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Mutation</subject><subject>Poly-ADP-Ribose Binding Proteins</subject><subject>strand break</subject><issn>1521-6543</issn><issn>1521-6551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90UlqHDEUBmARYuIhwTcIgiwSMO3oaSr1sj0bTLKJIbtCpXply66WOlKVQ3vlI_iMPonVeAgEEm2kxadfT_yEbAPbBcb4Vz82u1KqN2QDFIeJVgrevp6lWCebOV-xsio2fUfWOUhhAMwGuTnADt3gb5AmzLEfBx8DjR1dnPDZT9pF56kNLcVwaYPDlh58m9Emob22F0h9oIX7Wx8uaLKtt6vbD3f3QwFDwS66a7sMSPMytCnOke5Rh32f35O1zvYZPzzvW-T86PDH_snk7Pvx6f7sbOIkMDVpnXBWGF0hGqVFJw1UCixqrhoQUJmqmxrVqUpJ7pjiUyO0hJY1aKauka3YIp-fchcp_hoxD_Xc59UENmAcc200Z0xyXRX55b8SlJCGaSZNoZ_-oldxTKH8oyioRJlO6D9PuxRzTtjVi-TnNi1rYPWqtLqUVpfSivz4nDc2c2xf3UtLBew8gd--x-W_curT871V3CNkfZ64</recordid><startdate>201104</startdate><enddate>201104</enddate><creator>Ropolo, Monica</creator><creator>Cappelli, Enrico</creator><creator>Foresta, Mara</creator><creator>Poggi, Alessandro</creator><creator>Proietti‐De‐Santis, Luca</creator><creator>Frosina, Guido</creator><general>Wiley Subscription Services, Inc., a Wiley company</general><general>Wiley Subscription Services, Inc</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>201104</creationdate><title>Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation‐treated cockayne syndrome B cells</title><author>Ropolo, Monica ; Cappelli, Enrico ; Foresta, Mara ; Poggi, Alessandro ; Proietti‐De‐Santis, Luca ; Frosina, Guido</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4105-dc3ca3867ee8563f481751ae625b131787f985f57542c052983641d0be89cb4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Cell Line</topic><topic>Child, Preschool</topic><topic>Cockayne syndrome</topic><topic>Cockayne Syndrome - metabolism</topic><topic>Cockayne Syndrome - pathology</topic><topic>comet</topic><topic>DNA Breaks - radiation effects</topic><topic>DNA Helicases - genetics</topic><topic>DNA Helicases - metabolism</topic><topic>DNA Repair</topic><topic>DNA Repair Enzymes - genetics</topic><topic>DNA Repair Enzymes - metabolism</topic><topic>Female</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - radiation effects</topic><topic>Fluorescent Antibody Technique, Direct</topic><topic>H2AX</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Mutation</topic><topic>Poly-ADP-Ribose Binding Proteins</topic><topic>strand break</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ropolo, Monica</creatorcontrib><creatorcontrib>Cappelli, Enrico</creatorcontrib><creatorcontrib>Foresta, Mara</creatorcontrib><creatorcontrib>Poggi, Alessandro</creatorcontrib><creatorcontrib>Proietti‐De‐Santis, Luca</creatorcontrib><creatorcontrib>Frosina, Guido</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>IUBMB life</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ropolo, Monica</au><au>Cappelli, Enrico</au><au>Foresta, Mara</au><au>Poggi, Alessandro</au><au>Proietti‐De‐Santis, Luca</au><au>Frosina, Guido</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation‐treated cockayne syndrome B cells</atitle><jtitle>IUBMB life</jtitle><addtitle>IUBMB Life</addtitle><date>2011-04</date><risdate>2011</risdate><volume>63</volume><issue>4</issue><spage>272</spage><epage>276</epage><pages>272-276</pages><issn>1521-6543</issn><eissn>1521-6551</eissn><coden>IULIF8</coden><abstract>We have previously shown that DNA repair of oxidized bases (either purines or pyrimidines) is inefficient in cells from patients with Cockayne syndrome (cs), a rare developmental and neurological genetic disorder. Here, we show for the first time that resolution of ionizing radiation (IR)‐induced pH2AX foci, an indicator of DNA double‐strand breaks, is significantly delayed in IR‐treated cells belonging to the B complementation group of cs (csb). Using alkaline single‐cell gel electrophoresis, which predominantly detects single‐strand breaks, we further demonstrate elevated DNA breakage in csb cells early after irradiation. Both the delayed resolution of pH2AX foci and the early DNA breakage of csb cells were partially complemented by expression of wild‐type CSB protein. Hence, the csb mutation impairs resolution of pH2AX foci and causes DNA fragility, broadening the spectrum of lesions whose processing is altered in this syndrome. © 2011 IUBMB IUBMB Life, 63(4): 272–276, 2011</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., a Wiley company</pub><pmid>21438118</pmid><doi>10.1002/iub.445</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Cell Line Child, Preschool Cockayne syndrome Cockayne Syndrome - metabolism Cockayne Syndrome - pathology comet DNA Breaks - radiation effects DNA Helicases - genetics DNA Helicases - metabolism DNA Repair DNA Repair Enzymes - genetics DNA Repair Enzymes - metabolism Female Fibroblasts - metabolism Fibroblasts - radiation effects Fluorescent Antibody Technique, Direct H2AX Histones - metabolism Humans Kinetics Mutation Poly-ADP-Ribose Binding Proteins strand break |
| title | Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation‐treated cockayne syndrome B cells |
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