Coordination of Structure-Specific Nucleases by Human SLX4/BTBD12 Is Required for DNA Repair
Budding yeast Slx4 interacts with the structure-specific endonuclease Slx1 to ensure completion of ribosomal DNA replication. Slx4 also interacts with the Rad1-Rad10 endonuclease to control cleavage of 3′ flaps during repair of double-strand breaks (DSBs). Here we describe the identification of huma...
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| Veröffentlicht in: | Molecular cell 2009-07, Vol.35 (1), p.116-127 |
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| creator | Muñoz, Ivan M. Hain, Karolina Déclais, Anne-Cécile Gardiner, Mary Toh, Geraldine W. Sanchez-Pulido, Luis Heuckmann, Johannes M. Toth, Rachel Macartney, Thomas Eppink, Berina Kanaar, Roland Ponting, Chris P. Lilley, David M.J. Rouse, John |
| description | Budding yeast Slx4 interacts with the structure-specific endonuclease Slx1 to ensure completion of ribosomal DNA replication. Slx4 also interacts with the Rad1-Rad10 endonuclease to control cleavage of 3′ flaps during repair of double-strand breaks (DSBs). Here we describe the identification of human SLX4, a scaffold for DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1. SLX4 immunoprecipitates show SLX1-dependent nuclease activity toward Holliday junctions and MUS81-dependent activity toward other branched DNA structures. Furthermore, SLX4 enhances the nuclease activity of SLX1, MUS81, and XPF. Consistent with a role in processing recombination intermediates, cells depleted of SLX4 are hypersensitive to genotoxins that cause DSBs and show defects in the resolution of interstrand crosslink-induced DSBs. Depletion of SLX4 causes a decrease in DSB-induced homologous recombination. These data show that SLX4 is a regulator of structure-specific nucleases and that SLX4 and SLX1 are important regulators of genome stability in human cells. |
| doi_str_mv | 10.1016/j.molcel.2009.06.020 |
| format | Article |
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Slx4 also interacts with the Rad1-Rad10 endonuclease to control cleavage of 3′ flaps during repair of double-strand breaks (DSBs). Here we describe the identification of human SLX4, a scaffold for DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1. SLX4 immunoprecipitates show SLX1-dependent nuclease activity toward Holliday junctions and MUS81-dependent activity toward other branched DNA structures. Furthermore, SLX4 enhances the nuclease activity of SLX1, MUS81, and XPF. Consistent with a role in processing recombination intermediates, cells depleted of SLX4 are hypersensitive to genotoxins that cause DSBs and show defects in the resolution of interstrand crosslink-induced DSBs. Depletion of SLX4 causes a decrease in DSB-induced homologous recombination. These data show that SLX4 is a regulator of structure-specific nucleases and that SLX4 and SLX1 are important regulators of genome stability in human cells.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2009.06.020</identifier><identifier>PMID: 19595721</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Blotting, Western ; Cell Line ; Cell Line, Tumor ; DNA ; DNA Breaks, Double-Stranded ; DNA Repair ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Endonucleases - genetics ; Endonucleases - metabolism ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; Humans ; Immunoprecipitation ; Protein Binding ; Recombinases - genetics ; Recombinases - metabolism ; RNA, Small Interfering - genetics ; Transfection ; Two-Hybrid System Techniques</subject><ispartof>Molecular cell, 2009-07, Vol.35 (1), p.116-127</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-c1b60bb202087c802281397aba563368b12ee9dc72cc99103e4345a73cb309583</citedby><cites>FETCH-LOGICAL-c472t-c1b60bb202087c802281397aba563368b12ee9dc72cc99103e4345a73cb309583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S109727650900433X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19595721$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muñoz, Ivan M.</creatorcontrib><creatorcontrib>Hain, Karolina</creatorcontrib><creatorcontrib>Déclais, Anne-Cécile</creatorcontrib><creatorcontrib>Gardiner, Mary</creatorcontrib><creatorcontrib>Toh, Geraldine W.</creatorcontrib><creatorcontrib>Sanchez-Pulido, Luis</creatorcontrib><creatorcontrib>Heuckmann, Johannes M.</creatorcontrib><creatorcontrib>Toth, Rachel</creatorcontrib><creatorcontrib>Macartney, Thomas</creatorcontrib><creatorcontrib>Eppink, Berina</creatorcontrib><creatorcontrib>Kanaar, Roland</creatorcontrib><creatorcontrib>Ponting, Chris P.</creatorcontrib><creatorcontrib>Lilley, David M.J.</creatorcontrib><creatorcontrib>Rouse, John</creatorcontrib><title>Coordination of Structure-Specific Nucleases by Human SLX4/BTBD12 Is Required for DNA Repair</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>Budding yeast Slx4 interacts with the structure-specific endonuclease Slx1 to ensure completion of ribosomal DNA replication. Slx4 also interacts with the Rad1-Rad10 endonuclease to control cleavage of 3′ flaps during repair of double-strand breaks (DSBs). Here we describe the identification of human SLX4, a scaffold for DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1. SLX4 immunoprecipitates show SLX1-dependent nuclease activity toward Holliday junctions and MUS81-dependent activity toward other branched DNA structures. Furthermore, SLX4 enhances the nuclease activity of SLX1, MUS81, and XPF. Consistent with a role in processing recombination intermediates, cells depleted of SLX4 are hypersensitive to genotoxins that cause DSBs and show defects in the resolution of interstrand crosslink-induced DSBs. Depletion of SLX4 causes a decrease in DSB-induced homologous recombination. These data show that SLX4 is a regulator of structure-specific nucleases and that SLX4 and SLX1 are important regulators of genome stability in human cells.</description><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>DNA</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endonucleases - genetics</subject><subject>Endonucleases - metabolism</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Protein Binding</subject><subject>Recombinases - genetics</subject><subject>Recombinases - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>Transfection</subject><subject>Two-Hybrid System Techniques</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAUhYMovv-BSFbuWpM0TZqNoDM-BgYFR8GFENL0FjK0zZi0wvx7Kx1w5-peLuecy_kQuqAkpYSK63Xa-sZCkzJCVEpEShjZQ8eUKJlwKvj-bmdS5EfoJMY1IZTnhTpER1TlKpeMHqPPmfehcp3pne-wr_GqD4PthwDJagPW1c7i58E2YCJEXG7x09CaDq-WH_z67u1uThleRPwKX4MLUOHaBzx_vh0PG-PCGTqoTRPhfDdP0fvD_dvsKVm-PC5mt8vEcsn6xNJSkLJkY4FC2oIwVtBMSVOaXGSZKErKAFRlJbNWKUoy4BnPjcxsmRGVF9kpuppyN8F_DRB73bo4omlMB36IWkheqDF9FPJJaIOPMUCtN8G1Jmw1JfqXql7riar-paqJ0JPtcpc_lC1Uf6YdxlFwMwlgbPntIOhoHXQWqpGK7XXl3f8ffgAJsYf1</recordid><startdate>20090710</startdate><enddate>20090710</enddate><creator>Muñoz, Ivan M.</creator><creator>Hain, Karolina</creator><creator>Déclais, Anne-Cécile</creator><creator>Gardiner, Mary</creator><creator>Toh, Geraldine W.</creator><creator>Sanchez-Pulido, Luis</creator><creator>Heuckmann, Johannes M.</creator><creator>Toth, Rachel</creator><creator>Macartney, Thomas</creator><creator>Eppink, Berina</creator><creator>Kanaar, Roland</creator><creator>Ponting, Chris P.</creator><creator>Lilley, David M.J.</creator><creator>Rouse, John</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20090710</creationdate><title>Coordination of Structure-Specific Nucleases by Human SLX4/BTBD12 Is Required for DNA Repair</title><author>Muñoz, Ivan M. ; Hain, Karolina ; Déclais, Anne-Cécile ; Gardiner, Mary ; Toh, Geraldine W. ; Sanchez-Pulido, Luis ; Heuckmann, Johannes M. ; Toth, Rachel ; Macartney, Thomas ; Eppink, Berina ; Kanaar, Roland ; Ponting, Chris P. ; Lilley, David M.J. ; Rouse, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-c1b60bb202087c802281397aba563368b12ee9dc72cc99103e4345a73cb309583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>DNA</topic><topic>DNA Breaks, Double-Stranded</topic><topic>DNA Repair</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Endonucleases - genetics</topic><topic>Endonucleases - metabolism</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Protein Binding</topic><topic>Recombinases - genetics</topic><topic>Recombinases - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>Transfection</topic><topic>Two-Hybrid System Techniques</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muñoz, Ivan M.</creatorcontrib><creatorcontrib>Hain, Karolina</creatorcontrib><creatorcontrib>Déclais, Anne-Cécile</creatorcontrib><creatorcontrib>Gardiner, Mary</creatorcontrib><creatorcontrib>Toh, Geraldine W.</creatorcontrib><creatorcontrib>Sanchez-Pulido, Luis</creatorcontrib><creatorcontrib>Heuckmann, Johannes M.</creatorcontrib><creatorcontrib>Toth, Rachel</creatorcontrib><creatorcontrib>Macartney, Thomas</creatorcontrib><creatorcontrib>Eppink, Berina</creatorcontrib><creatorcontrib>Kanaar, Roland</creatorcontrib><creatorcontrib>Ponting, Chris P.</creatorcontrib><creatorcontrib>Lilley, David M.J.</creatorcontrib><creatorcontrib>Rouse, John</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muñoz, Ivan M.</au><au>Hain, Karolina</au><au>Déclais, Anne-Cécile</au><au>Gardiner, Mary</au><au>Toh, Geraldine W.</au><au>Sanchez-Pulido, Luis</au><au>Heuckmann, Johannes M.</au><au>Toth, Rachel</au><au>Macartney, Thomas</au><au>Eppink, Berina</au><au>Kanaar, Roland</au><au>Ponting, Chris P.</au><au>Lilley, David M.J.</au><au>Rouse, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coordination of Structure-Specific Nucleases by Human SLX4/BTBD12 Is Required for DNA Repair</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2009-07-10</date><risdate>2009</risdate><volume>35</volume><issue>1</issue><spage>116</spage><epage>127</epage><pages>116-127</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>Budding yeast Slx4 interacts with the structure-specific endonuclease Slx1 to ensure completion of ribosomal DNA replication. Slx4 also interacts with the Rad1-Rad10 endonuclease to control cleavage of 3′ flaps during repair of double-strand breaks (DSBs). Here we describe the identification of human SLX4, a scaffold for DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1. SLX4 immunoprecipitates show SLX1-dependent nuclease activity toward Holliday junctions and MUS81-dependent activity toward other branched DNA structures. Furthermore, SLX4 enhances the nuclease activity of SLX1, MUS81, and XPF. Consistent with a role in processing recombination intermediates, cells depleted of SLX4 are hypersensitive to genotoxins that cause DSBs and show defects in the resolution of interstrand crosslink-induced DSBs. Depletion of SLX4 causes a decrease in DSB-induced homologous recombination. 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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Blotting, Western Cell Line Cell Line, Tumor DNA DNA Breaks, Double-Stranded DNA Repair DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Endonucleases - genetics Endonucleases - metabolism Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Humans Immunoprecipitation Protein Binding Recombinases - genetics Recombinases - metabolism RNA, Small Interfering - genetics Transfection Two-Hybrid System Techniques |
| title | Coordination of Structure-Specific Nucleases by Human SLX4/BTBD12 Is Required for DNA Repair |
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