p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene
DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild‐type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the in vivo binding of wild‐type p53 to a p53 response element in the promoter of Rad51 a...
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| Veröffentlicht in: | EMBO reports 2006-02, Vol.7 (2), p.219-224 |
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| creator | Arias-Lopez, Carmen Lazaro-Trueba, Iciar Kerr, Peter Lord, Christopher J Dexter, Tim Iravani, Marjan Ashworth, Alan Silva, Augusto |
| description | DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild‐type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the
in vivo
binding of wild‐type p53 to a p53 response element in the promoter of Rad51 and the downregulation of Rad51 messenger RNA and protein by wild‐type p53, favoured by DNA damage. Moreover, wild‐type p53 inhibits Rad51 foci formation in response to double‐strand breaks, whereas p53 contact mutant R280K fails to repress Rad51 mRNA and protein expression and Rad51 foci formation. We propose that transcriptional repression of Rad51 by p53 participates in regulating homologous recombination, and impaired Rad51 repression by p53 mutants may contribute to malignant transformation. |
| doi_str_mv | 10.1038/sj.embor.7400587 |
| format | Article |
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in vivo
binding of wild‐type p53 to a p53 response element in the promoter of Rad51 and the downregulation of Rad51 messenger RNA and protein by wild‐type p53, favoured by DNA damage. Moreover, wild‐type p53 inhibits Rad51 foci formation in response to double‐strand breaks, whereas p53 contact mutant R280K fails to repress Rad51 mRNA and protein expression and Rad51 foci formation. We propose that transcriptional repression of Rad51 by p53 participates in regulating homologous recombination, and impaired Rad51 repression by p53 mutants may contribute to malignant transformation.</description><identifier>ISSN: 1469-221X</identifier><identifier>EISSN: 1469-3178</identifier><identifier>EISSN: 1469-221X</identifier><identifier>DOI: 10.1038/sj.embor.7400587</identifier><identifier>PMID: 16322760</identifier><identifier>CODEN: ERMEAX</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Blotting, Western ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Deoxyribonucleic acid ; DNA ; Fluorescent Antibody Technique, Indirect ; Fluorescent Dyes ; Genes, Reporter ; genome stability ; homologous recombination ; Humans ; Luciferases - analysis ; Luciferases - metabolism ; Microscopy, Fluorescence ; Mutants ; p53 ; Rad51 ; Rad51 Recombinase - genetics ; Rad51 Recombinase - metabolism ; Recombination, Genetic ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Scientific Report ; Scientific Reports ; Transcription, Genetic ; transcriptional repression ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>EMBO reports, 2006-02, Vol.7 (2), p.219-224</ispartof><rights>European Molecular Biology Organization 2006</rights><rights>Copyright © 2006 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Feb 2006</rights><rights>Copyright © 2006, European Molecular Biology Organization 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c7177-a05fcc6c2ac49ffd019e12cef615d2d5788f2d6d4ff5ddc45570c5df06351ac93</citedby><cites>FETCH-LOGICAL-c7177-a05fcc6c2ac49ffd019e12cef615d2d5788f2d6d4ff5ddc45570c5df06351ac93</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/PMC1369244/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1369244/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16322760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arias-Lopez, Carmen</creatorcontrib><creatorcontrib>Lazaro-Trueba, Iciar</creatorcontrib><creatorcontrib>Kerr, Peter</creatorcontrib><creatorcontrib>Lord, Christopher J</creatorcontrib><creatorcontrib>Dexter, Tim</creatorcontrib><creatorcontrib>Iravani, Marjan</creatorcontrib><creatorcontrib>Ashworth, Alan</creatorcontrib><creatorcontrib>Silva, Augusto</creatorcontrib><title>p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene</title><title>EMBO reports</title><addtitle>EMBO Rep</addtitle><addtitle>EMBO Rep</addtitle><description>DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild‐type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the
in vivo
binding of wild‐type p53 to a p53 response element in the promoter of Rad51 and the downregulation of Rad51 messenger RNA and protein by wild‐type p53, favoured by DNA damage. Moreover, wild‐type p53 inhibits Rad51 foci formation in response to double‐strand breaks, whereas p53 contact mutant R280K fails to repress Rad51 mRNA and protein expression and Rad51 foci formation. We propose that transcriptional repression of Rad51 by p53 participates in regulating homologous recombination, and impaired Rad51 repression by p53 mutants may contribute to malignant transformation.</description><subject>Blotting, Western</subject><subject>Cell Line, Tumor</subject><subject>Chromatin Immunoprecipitation</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Fluorescent Dyes</subject><subject>Genes, Reporter</subject><subject>genome stability</subject><subject>homologous recombination</subject><subject>Humans</subject><subject>Luciferases - analysis</subject><subject>Luciferases - metabolism</subject><subject>Microscopy, Fluorescence</subject><subject>Mutants</subject><subject>p53</subject><subject>Rad51</subject><subject>Rad51 Recombinase - genetics</subject><subject>Rad51 Recombinase - metabolism</subject><subject>Recombination, Genetic</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Scientific Report</subject><subject>Scientific Reports</subject><subject>Transcription, Genetic</subject><subject>transcriptional repression</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>1469-221X</issn><issn>1469-3178</issn><issn>1469-221X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkktv1DAUhS0Eog_YswFFLLrL4EdsxxukEkpBakGqgLKzPH5kMiTxYCfA_Hs8JJoBFnRly-c7x9f3GoAnCC4QJOWLuF7YbunDghcQ0pLfA8eoYCIniJf35z3G6MsROIlxDRMjePkQHCFGMOYMHoPPG0qyzpuxVYON2cp3vvW1H2MWrPbdsunV0Pg-W26zIag-6tBsdgeqTUC9c-1U77JhZbOb89cUZbXt7SPwwKk22sfzego-vbn4WL3Nrz5cvqvOr3LNEee5gtRpzTRWuhDOGYiERVhbxxA12FBelg4bZgrnqDG6oJRDTY2DjFCktCCn4OWUuxmXnTXa9qnKVm5C06mwlV418m-lb1ay9t8lIkzgokgBZ3NA8N9GGwfZNVHbtlW9TV2QjDNMC0juBJEoKSEQJfD5P-DajyE1LEoMS4oZEjRBcIJ08DEG6_YlIyh3o5VxLX-PVs6jTZZnfz71YJhnmQAxAT-a1m7vDJQX169uDuFo8sZk62sbDkX_p6Cnkyd9kTHY_YUHPZ_0Jg72515W4WvqKuFU3r6_lMV1dcsrIWRFfgHRdt4n</recordid><startdate>200602</startdate><enddate>200602</enddate><creator>Arias-Lopez, Carmen</creator><creator>Lazaro-Trueba, Iciar</creator><creator>Kerr, Peter</creator><creator>Lord, Christopher J</creator><creator>Dexter, Tim</creator><creator>Iravani, Marjan</creator><creator>Ashworth, Alan</creator><creator>Silva, Augusto</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200602</creationdate><title>p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene</title><author>Arias-Lopez, Carmen ; Lazaro-Trueba, Iciar ; Kerr, Peter ; Lord, Christopher J ; Dexter, Tim ; Iravani, Marjan ; Ashworth, Alan ; Silva, Augusto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c7177-a05fcc6c2ac49ffd019e12cef615d2d5788f2d6d4ff5ddc45570c5df06351ac93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Blotting, Western</topic><topic>Cell Line, Tumor</topic><topic>Chromatin Immunoprecipitation</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Fluorescent Dyes</topic><topic>Genes, Reporter</topic><topic>genome stability</topic><topic>homologous recombination</topic><topic>Humans</topic><topic>Luciferases - analysis</topic><topic>Luciferases - metabolism</topic><topic>Microscopy, Fluorescence</topic><topic>Mutants</topic><topic>p53</topic><topic>Rad51</topic><topic>Rad51 Recombinase - genetics</topic><topic>Rad51 Recombinase - metabolism</topic><topic>Recombination, Genetic</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Scientific Report</topic><topic>Scientific Reports</topic><topic>Transcription, Genetic</topic><topic>transcriptional repression</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arias-Lopez, Carmen</creatorcontrib><creatorcontrib>Lazaro-Trueba, Iciar</creatorcontrib><creatorcontrib>Kerr, Peter</creatorcontrib><creatorcontrib>Lord, Christopher J</creatorcontrib><creatorcontrib>Dexter, Tim</creatorcontrib><creatorcontrib>Iravani, Marjan</creatorcontrib><creatorcontrib>Ashworth, Alan</creatorcontrib><creatorcontrib>Silva, Augusto</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>EMBO reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arias-Lopez, Carmen</au><au>Lazaro-Trueba, Iciar</au><au>Kerr, Peter</au><au>Lord, Christopher J</au><au>Dexter, Tim</au><au>Iravani, Marjan</au><au>Ashworth, Alan</au><au>Silva, Augusto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene</atitle><jtitle>EMBO reports</jtitle><stitle>EMBO Rep</stitle><addtitle>EMBO Rep</addtitle><date>2006-02</date><risdate>2006</risdate><volume>7</volume><issue>2</issue><spage>219</spage><epage>224</epage><pages>219-224</pages><issn>1469-221X</issn><eissn>1469-3178</eissn><eissn>1469-221X</eissn><coden>ERMEAX</coden><abstract>DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild‐type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the
in vivo
binding of wild‐type p53 to a p53 response element in the promoter of Rad51 and the downregulation of Rad51 messenger RNA and protein by wild‐type p53, favoured by DNA damage. Moreover, wild‐type p53 inhibits Rad51 foci formation in response to double‐strand breaks, whereas p53 contact mutant R280K fails to repress Rad51 mRNA and protein expression and Rad51 foci formation. We propose that transcriptional repression of Rad51 by p53 participates in regulating homologous recombination, and impaired Rad51 repression by p53 mutants may contribute to malignant transformation.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>16322760</pmid><doi>10.1038/sj.embor.7400587</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Blotting, Western Cell Line, Tumor Chromatin Immunoprecipitation Deoxyribonucleic acid DNA Fluorescent Antibody Technique, Indirect Fluorescent Dyes Genes, Reporter genome stability homologous recombination Humans Luciferases - analysis Luciferases - metabolism Microscopy, Fluorescence Mutants p53 Rad51 Rad51 Recombinase - genetics Rad51 Recombinase - metabolism Recombination, Genetic Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Scientific Report Scientific Reports Transcription, Genetic transcriptional repression Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism |
| title | p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene |
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