CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes
Histone acetylation at DNA double-strand break (DSB) sites by CBP and p300 histone acetyltransferases (HATs) is critical for the recruitment of DSB repair proteins to chromatin. Here, we show that CBP and p300 HATs also function in DSB repair by transcriptionally activating the BRCA1 and RAD51 genes...
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| description | Histone acetylation at DNA double-strand break (DSB) sites by CBP and p300 histone acetyltransferases (HATs) is critical for the recruitment of DSB repair proteins to chromatin. Here, we show that CBP and p300 HATs also function in DSB repair by transcriptionally activating the BRCA1 and RAD51 genes, which are involved in homologous recombination (HR), a major DSB repair system. siRNA-mediated depletion of CBP and p300 impaired HR activity and downregulated BRCA1 and RAD51 at the protein and mRNA levels. Chromatin immunoprecipitation assays showed that CBP and p300 bind to the promoter regions of the BRCA1 and RAD51 genes, and that depletion of CBP and/or p300 reduces H3 and H4 acetylation and inhibits binding of the transcription factor E2F1 to these promoters. Depletion of CBP and p300 impaired DNA damage-induced phosphorylation and chromatin binding of the single-strand DNA-binding protein RPA following BRCA1-mediated DNA end resection. Consistent with this, subsequent phosphorylation of CHK1 and activation of the G2/M damage checkpoint were also impaired. These results indicate that the HATs CBP and p300 play multiple roles in the activation of the cellular response to DSBs. |
| doi_str_mv | 10.1371/journal.pone.0052810 |
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Here, we show that CBP and p300 HATs also function in DSB repair by transcriptionally activating the BRCA1 and RAD51 genes, which are involved in homologous recombination (HR), a major DSB repair system. siRNA-mediated depletion of CBP and p300 impaired HR activity and downregulated BRCA1 and RAD51 at the protein and mRNA levels. Chromatin immunoprecipitation assays showed that CBP and p300 bind to the promoter regions of the BRCA1 and RAD51 genes, and that depletion of CBP and/or p300 reduces H3 and H4 acetylation and inhibits binding of the transcription factor E2F1 to these promoters. Depletion of CBP and p300 impaired DNA damage-induced phosphorylation and chromatin binding of the single-strand DNA-binding protein RPA following BRCA1-mediated DNA end resection. Consistent with this, subsequent phosphorylation of CHK1 and activation of the G2/M damage checkpoint were also impaired. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>2012 Ogiwara, Kohno 2012 Ogiwara, Kohno</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-db15b74195134bf2569c35fbc6376691017fc09c97c6ae41752607a19e74ad043</citedby><cites>FETCH-LOGICAL-c758t-db15b74195134bf2569c35fbc6376691017fc09c97c6ae41752607a19e74ad043</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/PMC3527616/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527616/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23285190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ogiwara, Hideaki</creatorcontrib><creatorcontrib>Kohno, Takashi</creatorcontrib><title>CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Histone acetylation at DNA double-strand break (DSB) sites by CBP and p300 histone acetyltransferases (HATs) is critical for the recruitment of DSB repair proteins to chromatin. Here, we show that CBP and p300 HATs also function in DSB repair by transcriptionally activating the BRCA1 and RAD51 genes, which are involved in homologous recombination (HR), a major DSB repair system. siRNA-mediated depletion of CBP and p300 impaired HR activity and downregulated BRCA1 and RAD51 at the protein and mRNA levels. Chromatin immunoprecipitation assays showed that CBP and p300 bind to the promoter regions of the BRCA1 and RAD51 genes, and that depletion of CBP and/or p300 reduces H3 and H4 acetylation and inhibits binding of the transcription factor E2F1 to these promoters. Depletion of CBP and p300 impaired DNA damage-induced phosphorylation and chromatin binding of the single-strand DNA-binding protein RPA following BRCA1-mediated DNA end resection. Consistent with this, subsequent phosphorylation of CHK1 and activation of the G2/M damage checkpoint were also impaired. These results indicate that the HATs CBP and p300 play multiple roles in the activation of the cellular response to DSBs.</description><subject>Acetylation</subject><subject>Activation</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>BRCA1 protein</subject><subject>BRCA1 Protein - genetics</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Checkpoint Kinase 1</subject><subject>CHK1 protein</subject><subject>Chromatin</subject><subject>CREB-Binding Protein - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>Depletion</subject><subject>DNA</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA damage</subject><subject>DNA repair</subject><subject>DNA-binding protein</subject><subject>Double-strand break repair</subject><subject>E2F1 Transcription Factor</subject><subject>Event-related potentials</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genomes</subject><subject>Histones - metabolism</subject><subject>Homologous Recombination</subject><subject>Homology</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Ionizing radiation</subject><subject>Outerwear</subject><subject>p300-CBP Transcription Factors - metabolism</subject><subject>Phosphorylation</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Protein Kinases - metabolism</subject><subject>Proteins</subject><subject>Rad51 Recombinase - genetics</subject><subject>Recruitment</subject><subject>Repair</subject><subject>Replication Protein A - metabolism</subject><subject>RNA</subject><subject>Signal Transduction</subject><subject>siRNA</subject><subject>Transcription (Genetics)</subject><subject>Transcription factors</subject><subject>Transcriptional Activation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYQkJw0WLHsR3fIHXla9KkofFxaznuSerJjYvtTPQf8LNx22xa0S5QLhwdP-c99utziuI5wVNCBXl35YfQazdd-x6mGLOyJvhBcUwkLSe8xPThnf-j4kmMVxmiNeePi6OSljUjEh8Xf-anX5HuF2hNMUZLG1OWQ9pA2rgUdB9bCDpCRMb3KdhmSICSR0u_8s53fogogPGrxvY6Wd-jZoN2aSbY9TagndtkuWSv837fobQEdHo5n5Fd0cvZB0ZQBz3Ep8WjVrsIz8b1pPjx6eP3-ZfJ-cXns_nsfGIEq9Nk0RDWiIpIRmjVtCXj0lDWNoZTwbkkmIjWYGmkMFxDRQQrORaaSBCVXuCKnhQv97pr56MaTYyK0FIQmd2RmTjbEwuvr9Q62JUOG-W1VbuAD53SIVnjQBnJhax1Pg_UVclbrQWlrKm4hLptRJO13o_VhmYFCwPZRO0ORA93ertUnb9WlJWCE54F3owCwf8aICa1stGAc7qH7L4ipaBEVLxkGX31D3r_7Uaq0_kCtm99rmu2ompWCYFZzQnJ1PQeKn8LWNncCtDaHD9IeHuQsG0X-J06PcSozr5d_j978fOQfX2HXYJ2aRm9G7a9FQ_Bag-a4GMM0N6aTLDaDsyNG2o7MGocmJz24u4D3SbdTAj9C2SfD_M</recordid><startdate>20121220</startdate><enddate>20121220</enddate><creator>Ogiwara, Hideaki</creator><creator>Kohno, Takashi</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>IOV</scope><scope>ISR</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>AEUYN</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121220</creationdate><title>CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes</title><author>Ogiwara, Hideaki ; Kohno, Takashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-db15b74195134bf2569c35fbc6376691017fc09c97c6ae41752607a19e74ad043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acetylation</topic><topic>Activation</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>BRCA1 protein</topic><topic>BRCA1 Protein - genetics</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Checkpoint Kinase 1</topic><topic>CHK1 protein</topic><topic>Chromatin</topic><topic>CREB-Binding Protein - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>Depletion</topic><topic>DNA</topic><topic>DNA Breaks, Double-Stranded</topic><topic>DNA damage</topic><topic>DNA repair</topic><topic>DNA-binding protein</topic><topic>Double-strand break repair</topic><topic>E2F1 Transcription Factor</topic><topic>Event-related potentials</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genomes</topic><topic>Histones - metabolism</topic><topic>Homologous Recombination</topic><topic>Homology</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Ionizing radiation</topic><topic>Outerwear</topic><topic>p300-CBP Transcription Factors - metabolism</topic><topic>Phosphorylation</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding</topic><topic>Protein Kinases - 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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>Ogiwara, Hideaki</au><au>Kohno, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-20</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e52810</spage><epage>e52810</epage><pages>e52810-e52810</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Histone acetylation at DNA double-strand break (DSB) sites by CBP and p300 histone acetyltransferases (HATs) is critical for the recruitment of DSB repair proteins to chromatin. Here, we show that CBP and p300 HATs also function in DSB repair by transcriptionally activating the BRCA1 and RAD51 genes, which are involved in homologous recombination (HR), a major DSB repair system. siRNA-mediated depletion of CBP and p300 impaired HR activity and downregulated BRCA1 and RAD51 at the protein and mRNA levels. Chromatin immunoprecipitation assays showed that CBP and p300 bind to the promoter regions of the BRCA1 and RAD51 genes, and that depletion of CBP and/or p300 reduces H3 and H4 acetylation and inhibits binding of the transcription factor E2F1 to these promoters. Depletion of CBP and p300 impaired DNA damage-induced phosphorylation and chromatin binding of the single-strand DNA-binding protein RPA following BRCA1-mediated DNA end resection. Consistent with this, subsequent phosphorylation of CHK1 and activation of the G2/M damage checkpoint were also impaired. These results indicate that the HATs CBP and p300 play multiple roles in the activation of the cellular response to DSBs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23285190</pmid><doi>10.1371/journal.pone.0052810</doi><tpages>e52810</tpages><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acetylation Activation Biology Biotechnology BRCA1 protein BRCA1 Protein - genetics Breast cancer Cancer Cell cycle Cell Line, Tumor Checkpoint Kinase 1 CHK1 protein Chromatin CREB-Binding Protein - metabolism Deoxyribonucleic acid Depletion DNA DNA Breaks, Double-Stranded DNA damage DNA repair DNA-binding protein Double-strand break repair E2F1 Transcription Factor Event-related potentials Gene expression Gene Expression Regulation, Neoplastic Genes Genomes Histones - metabolism Homologous Recombination Homology Humans Immunoprecipitation Ionizing radiation Outerwear p300-CBP Transcription Factors - metabolism Phosphorylation Promoter Regions, Genetic Protein Binding Protein Kinases - metabolism Proteins Rad51 Recombinase - genetics Recruitment Repair Replication Protein A - metabolism RNA Signal Transduction siRNA Transcription (Genetics) Transcription factors Transcriptional Activation |
| title | CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes |
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