The RSF1 histone-remodelling factor facilitates DNA double-strand break repair by recruiting centromeric and Fanconi Anaemia proteins
ATM is a central regulator of the cellular responses to DNA double-strand breaks (DSBs). Here we identify a biochemical interaction between ATM and RSF1 and we characterise the role of RSF1 in this response. The ATM-RSF1 interaction is dependent upon both DSBs and ATM kinase activity. Together with...
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| description | ATM is a central regulator of the cellular responses to DNA double-strand breaks (DSBs). Here we identify a biochemical interaction between ATM and RSF1 and we characterise the role of RSF1 in this response. The ATM-RSF1 interaction is dependent upon both DSBs and ATM kinase activity. Together with SNF2H/SMARCA5, RSF1 forms the RSF chromatin-remodelling complex. Although RSF1 is specific to the RSF complex, SNF2H/SMARCA5 is a catalytic subunit of several other chromatin-remodelling complexes. Although not required for checkpoint signalling, RSF1 is required for efficient repair of DSBs via both end-joining and homology-directed repair. Specifically, the ATM-dependent recruitment to sites of DSBs of the histone fold proteins CENPS/MHF1 and CENPX/MHF2, previously identified at centromeres, is RSF1-dependent. In turn these proteins recruit and regulate the mono-ubiquitination of the Fanconi Anaemia proteins FANCD2 and FANCI. We propose that by depositing CENPS/MHF1 and CENPX/MHF2, the RSF complex either directly or indirectly contributes to the reorganisation of chromatin around DSBs that is required for efficient DNA repair. |
| doi_str_mv | 10.1371/journal.pbio.1001856 |
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Here we identify a biochemical interaction between ATM and RSF1 and we characterise the role of RSF1 in this response. The ATM-RSF1 interaction is dependent upon both DSBs and ATM kinase activity. Together with SNF2H/SMARCA5, RSF1 forms the RSF chromatin-remodelling complex. Although RSF1 is specific to the RSF complex, SNF2H/SMARCA5 is a catalytic subunit of several other chromatin-remodelling complexes. Although not required for checkpoint signalling, RSF1 is required for efficient repair of DSBs via both end-joining and homology-directed repair. Specifically, the ATM-dependent recruitment to sites of DSBs of the histone fold proteins CENPS/MHF1 and CENPX/MHF2, previously identified at centromeres, is RSF1-dependent. In turn these proteins recruit and regulate the mono-ubiquitination of the Fanconi Anaemia proteins FANCD2 and FANCI. We propose that by depositing CENPS/MHF1 and CENPX/MHF2, the RSF complex either directly or indirectly contributes to the reorganisation of chromatin around DSBs that is required for efficient DNA repair.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.1001856</identifier><identifier>PMID: 24800743</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenosine Triphosphatases - genetics ; Adenosine Triphosphatases - metabolism ; Animals ; Ataxia Telangiectasia Mutated Proteins - genetics ; Ataxia Telangiectasia Mutated Proteins - metabolism ; B-Lymphocytes - cytology ; B-Lymphocytes - metabolism ; Biology and Life Sciences ; Cell Line, Tumor ; Centromeres ; Chickens ; Chromatin - chemistry ; Chromatin - metabolism ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomal Proteins, Non-Histone - metabolism ; DNA - genetics ; DNA - metabolism ; DNA Breaks, Double-Stranded ; DNA damage ; DNA End-Joining Repair ; DNA repair ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Fanconi Anemia Complementation Group D2 Protein - genetics ; Fanconi Anemia Complementation Group D2 Protein - metabolism ; Fanconi Anemia Complementation Group Proteins - genetics ; Fanconi Anemia Complementation Group Proteins - metabolism ; Gene Expression Regulation ; Genetic disorders ; Health aspects ; Histones ; Histones - genetics ; Histones - metabolism ; Humans ; Kinases ; Medical research ; Mutation ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Physiological aspects ; Protein research ; Recombinational DNA Repair ; Signal Transduction ; Trans-Activators - genetics ; Trans-Activators - metabolism</subject><ispartof>PLoS biology, 2014-05, Vol.12 (5), p.e1001856-e1001856</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Pessina, Lowndes 2014 Pessina, Lowndes</rights><rights>2014 Pessina, Lowndes. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Pessina F, Lowndes NF (2014) The RSF1 Histone-Remodelling Factor Facilitates DNA Double-Strand Break Repair by Recruiting Centromeric and Fanconi Anaemia Proteins. 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Here we identify a biochemical interaction between ATM and RSF1 and we characterise the role of RSF1 in this response. The ATM-RSF1 interaction is dependent upon both DSBs and ATM kinase activity. Together with SNF2H/SMARCA5, RSF1 forms the RSF chromatin-remodelling complex. Although RSF1 is specific to the RSF complex, SNF2H/SMARCA5 is a catalytic subunit of several other chromatin-remodelling complexes. Although not required for checkpoint signalling, RSF1 is required for efficient repair of DSBs via both end-joining and homology-directed repair. Specifically, the ATM-dependent recruitment to sites of DSBs of the histone fold proteins CENPS/MHF1 and CENPX/MHF2, previously identified at centromeres, is RSF1-dependent. In turn these proteins recruit and regulate the mono-ubiquitination of the Fanconi Anaemia proteins FANCD2 and FANCI. We propose that by depositing CENPS/MHF1 and CENPX/MHF2, the RSF complex either directly or indirectly contributes to the reorganisation of chromatin around DSBs that is required for efficient DNA repair.</description><subject>Adenosine Triphosphatases - genetics</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Animals</subject><subject>Ataxia Telangiectasia Mutated Proteins - genetics</subject><subject>Ataxia Telangiectasia Mutated Proteins - metabolism</subject><subject>B-Lymphocytes - cytology</subject><subject>B-Lymphocytes - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Cell Line, Tumor</subject><subject>Centromeres</subject><subject>Chickens</subject><subject>Chromatin - chemistry</subject><subject>Chromatin - metabolism</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA damage</subject><subject>DNA End-Joining Repair</subject><subject>DNA repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>Fanconi Anemia Complementation Group D2 Protein - genetics</subject><subject>Fanconi Anemia Complementation Group D2 Protein - metabolism</subject><subject>Fanconi Anemia Complementation Group Proteins - genetics</subject><subject>Fanconi Anemia Complementation Group Proteins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Genetic disorders</subject><subject>Health aspects</subject><subject>Histones</subject><subject>Histones - genetics</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Mutation</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Physiological aspects</subject><subject>Protein research</subject><subject>Recombinational DNA Repair</subject><subject>Signal Transduction</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVk89u1DAQxiMEomXhDRBE4gKHLP4X27kgrQoLK1Wt1BauluNMdl2SeLEdRB-A98bpbquuxAHkg0f27_vGmvFk2UuM5pgK_P7ajX7Q3XxbWzfHCGFZ8kfZMS5ZWQgpy8cP4qPsWQjXCBFSEfk0OyJMIiQYPc5-X20gv7hc4nxjQ3QDFB5610DX2WGdt9pE56fNdjbqCCH_eLbIGzfWHRQhej00ee1Bf889bLX1eX2TIuNHGye9gSF614O3Jp_QpR6MG2y-GDT0Vudb7yLYITzPnrS6C_Biv8-yr8tPVydfitPzz6uTxWlhBJax4FVd8aZkLbTCkJbSFmpODOOcg-SsZbUW3FBZATaN4ISBAZxiWWFaMS3oLHu98912Lqh9BYPCJeUouTCSiNWOaJy-Vltve-1vlNNW3R44v1baR2s6UJrysgZMGxDApOY1RUY0UAuOSopkk7w-7LONdQ_NbTF0d2B6eDPYjVq7n4ohjLngyeDt3sC7HyOEqHobTOqNHsCN07sJ4RLLlG-Wvdmha52eZofWJUcz4WpBJZFIIFIlav4XKq0mtSN1Blqbzg8E7w4EiYnwK671GIJaXV78B3v27-z5t0OW7VjjXQge2vsKYqSmUbhrpJpGQe1HIclePaz-veju79M_Ep0GBQ</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Pessina, Fabio</creator><creator>Lowndes, Noel F</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>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope></search><sort><creationdate>20140501</creationdate><title>The RSF1 histone-remodelling factor facilitates DNA double-strand break repair by recruiting centromeric and Fanconi Anaemia proteins</title><author>Pessina, Fabio ; Lowndes, Noel F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c718t-69b96d54fef7c2f33feb62c4666e864f4ba76c389e1cd7624ece1e1c891394a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenosine Triphosphatases - genetics</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>Animals</topic><topic>Ataxia Telangiectasia Mutated Proteins - genetics</topic><topic>Ataxia Telangiectasia Mutated Proteins - metabolism</topic><topic>B-Lymphocytes - cytology</topic><topic>B-Lymphocytes - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Cell Line, Tumor</topic><topic>Centromeres</topic><topic>Chickens</topic><topic>Chromatin - chemistry</topic><topic>Chromatin - metabolism</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosomal Proteins, Non-Histone - metabolism</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA Breaks, Double-Stranded</topic><topic>DNA damage</topic><topic>DNA End-Joining Repair</topic><topic>DNA repair</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>Fanconi Anemia Complementation Group D2 Protein - genetics</topic><topic>Fanconi Anemia Complementation Group D2 Protein - metabolism</topic><topic>Fanconi Anemia Complementation Group Proteins - genetics</topic><topic>Fanconi Anemia Complementation Group Proteins - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Genetic disorders</topic><topic>Health aspects</topic><topic>Histones</topic><topic>Histones - genetics</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Kinases</topic><topic>Medical research</topic><topic>Mutation</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Physiological aspects</topic><topic>Protein research</topic><topic>Recombinational DNA Repair</topic><topic>Signal Transduction</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pessina, Fabio</creatorcontrib><creatorcontrib>Lowndes, Noel F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pessina, Fabio</au><au>Lowndes, Noel F</au><au>Pellman, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The RSF1 histone-remodelling factor facilitates DNA double-strand break repair by recruiting centromeric and Fanconi Anaemia proteins</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>12</volume><issue>5</issue><spage>e1001856</spage><epage>e1001856</epage><pages>e1001856-e1001856</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>ATM is a central regulator of the cellular responses to DNA double-strand breaks (DSBs). Here we identify a biochemical interaction between ATM and RSF1 and we characterise the role of RSF1 in this response. The ATM-RSF1 interaction is dependent upon both DSBs and ATM kinase activity. Together with SNF2H/SMARCA5, RSF1 forms the RSF chromatin-remodelling complex. Although RSF1 is specific to the RSF complex, SNF2H/SMARCA5 is a catalytic subunit of several other chromatin-remodelling complexes. Although not required for checkpoint signalling, RSF1 is required for efficient repair of DSBs via both end-joining and homology-directed repair. Specifically, the ATM-dependent recruitment to sites of DSBs of the histone fold proteins CENPS/MHF1 and CENPX/MHF2, previously identified at centromeres, is RSF1-dependent. In turn these proteins recruit and regulate the mono-ubiquitination of the Fanconi Anaemia proteins FANCD2 and FANCI. We propose that by depositing CENPS/MHF1 and CENPX/MHF2, the RSF complex either directly or indirectly contributes to the reorganisation of chromatin around DSBs that is required for efficient DNA repair.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24800743</pmid><doi>10.1371/journal.pbio.1001856</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine Triphosphatases - genetics Adenosine Triphosphatases - metabolism Animals Ataxia Telangiectasia Mutated Proteins - genetics Ataxia Telangiectasia Mutated Proteins - metabolism B-Lymphocytes - cytology B-Lymphocytes - metabolism Biology and Life Sciences Cell Line, Tumor Centromeres Chickens Chromatin - chemistry Chromatin - metabolism Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - metabolism DNA - genetics DNA - metabolism DNA Breaks, Double-Stranded DNA damage DNA End-Joining Repair DNA repair DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Epithelial Cells - cytology Epithelial Cells - metabolism Fanconi Anemia Complementation Group D2 Protein - genetics Fanconi Anemia Complementation Group D2 Protein - metabolism Fanconi Anemia Complementation Group Proteins - genetics Fanconi Anemia Complementation Group Proteins - metabolism Gene Expression Regulation Genetic disorders Health aspects Histones Histones - genetics Histones - metabolism Humans Kinases Medical research Mutation Nuclear Proteins - genetics Nuclear Proteins - metabolism Physiological aspects Protein research Recombinational DNA Repair Signal Transduction Trans-Activators - genetics Trans-Activators - metabolism |
| title | The RSF1 histone-remodelling factor facilitates DNA double-strand break repair by recruiting centromeric and Fanconi Anaemia proteins |
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