XRN2 Links RNA:DNA Hybrid Resolution to Double Strand Break Repair Pathway Choice
It was recently shown that the 5’ to 3’ exoribonuclease XRN2 is involved in the DNA damage response. Importantly, loss of XRN2 abrogates DNA double stranded break repair via the non-homologous end-joining pathway. However, the mechanistic details of how XRN2 functions in the non-homologous end-joini...
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| Veröffentlicht in: | Cancers 2020-07, Vol.12 (7), p.1821 |
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| creator | Dang, Tuyen T. Morales, Julio C. |
| description | It was recently shown that the 5’ to 3’ exoribonuclease XRN2 is involved in the DNA damage response. Importantly, loss of XRN2 abrogates DNA double stranded break repair via the non-homologous end-joining pathway. However, the mechanistic details of how XRN2 functions in the non-homologous end-joining repair process are unknown. In this study, we elucidated that XRN2-mediated RNA:DNA hybrid resolution is required to allow Ku70 binding to DNA ends. These data suggest that XRN2 is required for the initiation of non-homologous end-joining repair. Interestingly, we uncovered a role for XRN2 in the homologous recombination repair pathway. Loss of XRN2 lead to a decrease in the repair of double strand breaks by homologous recombination. Strikingly, when we removed RNA:DNA hybrids by RNaseH1 over-expression, homologous recombination was not restored. We found RNA:DNA hybrid formation at and downstream of the DSB site, suggesting that unregulated transcription inhibits homologous recombination repair. In summary, our results indicate a relation between RNA:DNA hybrid resolution and double strand break repair pathway choice. |
| doi_str_mv | 10.3390/cancers12071821 |
| format | Article |
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Importantly, loss of XRN2 abrogates DNA double stranded break repair via the non-homologous end-joining pathway. However, the mechanistic details of how XRN2 functions in the non-homologous end-joining repair process are unknown. In this study, we elucidated that XRN2-mediated RNA:DNA hybrid resolution is required to allow Ku70 binding to DNA ends. These data suggest that XRN2 is required for the initiation of non-homologous end-joining repair. Interestingly, we uncovered a role for XRN2 in the homologous recombination repair pathway. Loss of XRN2 lead to a decrease in the repair of double strand breaks by homologous recombination. Strikingly, when we removed RNA:DNA hybrids by RNaseH1 over-expression, homologous recombination was not restored. We found RNA:DNA hybrid formation at and downstream of the DSB site, suggesting that unregulated transcription inhibits homologous recombination repair. In summary, our results indicate a relation between RNA:DNA hybrid resolution and double strand break repair pathway choice.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12071821</identifier><identifier>PMID: 32645903</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antibodies ; Cell cycle ; Defects ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA repair ; Double-strand break repair ; Gene loci ; Genomes ; Homologous recombination ; Homologous recombination repair ; Hybrids ; Non-homologous end joining ; Overexpression ; Ribonucleic acid ; RNA ; RNA polymerase ; Transcription</subject><ispartof>Cancers, 2020-07, Vol.12 (7), p.1821</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-27a7f856a085d6966039c6c1e2153e606f19fb89375ef5a480c62aa86128c6ac3</citedby><cites>FETCH-LOGICAL-c398t-27a7f856a085d6966039c6c1e2153e606f19fb89375ef5a480c62aa86128c6ac3</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/PMC7408924/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408924/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Dang, Tuyen T.</creatorcontrib><creatorcontrib>Morales, Julio C.</creatorcontrib><title>XRN2 Links RNA:DNA Hybrid Resolution to Double Strand Break Repair Pathway Choice</title><title>Cancers</title><description>It was recently shown that the 5’ to 3’ exoribonuclease XRN2 is involved in the DNA damage response. 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In summary, our results indicate a relation between RNA:DNA hybrid resolution and double strand break repair pathway choice.</description><subject>Antibodies</subject><subject>Cell cycle</subject><subject>Defects</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA repair</subject><subject>Double-strand break repair</subject><subject>Gene loci</subject><subject>Genomes</subject><subject>Homologous recombination</subject><subject>Homologous recombination repair</subject><subject>Hybrids</subject><subject>Non-homologous end joining</subject><subject>Overexpression</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA polymerase</subject><subject>Transcription</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><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>eNpdkc1LAzEQxYMoKurZa8CLl9p8bGYTD0Jt_YJStSp4C2matdHtpia7Sv97t1hEncs8mB-PNzyEDik54VyRrjWVdTFRRnIqGd1Au61iHQCVbf7SO-ggpVfSDuc0h3wb7XAGmVCE76L75_GI4aGv3hIej3qng1EPXy8n0U_x2KVQNrUPFa4DHoRmUjr8UEdTTfF5dOatJRbGR3xn6tmnWeL-LHjr9tFWYcrkDtZ7Dz1dXjz2rzvD26ubfm_YsVzJusNykxdSgCFSTEEBEK4sWOoYFdwBgYKqYiIVz4UrhMkkscCMkUCZtGAs30Nn376LZjJ3U-uqNlqpF9HPTVzqYLz-e6n8TL-ED51nRCqWtQbHa4MY3huXaj33ybqyNJULTdIsY5wAF2SFHv1DX0MTq_a9FcUUESCgpbrflI0hpeiKnzCU6FVj-l9j_AtTSYa1</recordid><startdate>20200707</startdate><enddate>20200707</enddate><creator>Dang, Tuyen T.</creator><creator>Morales, Julio C.</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200707</creationdate><title>XRN2 Links RNA:DNA Hybrid Resolution to Double Strand Break Repair Pathway Choice</title><author>Dang, Tuyen T. ; Morales, Julio C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-27a7f856a085d6966039c6c1e2153e606f19fb89375ef5a480c62aa86128c6ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibodies</topic><topic>Cell cycle</topic><topic>Defects</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA repair</topic><topic>Double-strand break repair</topic><topic>Gene loci</topic><topic>Genomes</topic><topic>Homologous recombination</topic><topic>Homologous recombination repair</topic><topic>Hybrids</topic><topic>Non-homologous end joining</topic><topic>Overexpression</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA polymerase</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dang, Tuyen T.</creatorcontrib><creatorcontrib>Morales, Julio C.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</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>ProQuest One Community College</collection><collection>ProQuest Central Korea</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 Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</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 China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dang, Tuyen T.</au><au>Morales, Julio C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>XRN2 Links RNA:DNA Hybrid Resolution to Double Strand Break Repair Pathway Choice</atitle><jtitle>Cancers</jtitle><date>2020-07-07</date><risdate>2020</risdate><volume>12</volume><issue>7</issue><spage>1821</spage><pages>1821-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>It was recently shown that the 5’ to 3’ exoribonuclease XRN2 is involved in the DNA damage response. Importantly, loss of XRN2 abrogates DNA double stranded break repair via the non-homologous end-joining pathway. However, the mechanistic details of how XRN2 functions in the non-homologous end-joining repair process are unknown. In this study, we elucidated that XRN2-mediated RNA:DNA hybrid resolution is required to allow Ku70 binding to DNA ends. These data suggest that XRN2 is required for the initiation of non-homologous end-joining repair. Interestingly, we uncovered a role for XRN2 in the homologous recombination repair pathway. Loss of XRN2 lead to a decrease in the repair of double strand breaks by homologous recombination. Strikingly, when we removed RNA:DNA hybrids by RNaseH1 over-expression, homologous recombination was not restored. We found RNA:DNA hybrid formation at and downstream of the DSB site, suggesting that unregulated transcription inhibits homologous recombination repair. 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| source | PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Antibodies Cell cycle Defects Deoxyribonucleic acid DNA DNA damage DNA repair Double-strand break repair Gene loci Genomes Homologous recombination Homologous recombination repair Hybrids Non-homologous end joining Overexpression Ribonucleic acid RNA RNA polymerase Transcription |
| title | XRN2 Links RNA:DNA Hybrid Resolution to Double Strand Break Repair Pathway Choice |
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