CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection
Double-strand breaks repaired by homologous recombination (HR) are first resected to form single-stranded DNA, which binds replication protein A (RPA). RPA attracts mediators that load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nu...
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| Veröffentlicht in: | Nature communications 2016-04, Vol.7, p.11364-11364 |
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| creator | Zeng, Ming Ren, Laifeng Mizuno, Ken'Ichi Nestoras, Konstantinos Wang, Haibin Tang, Zizhi Guo, Liandi Kong, Daochun Hu, Qiwen He, Qun Du, Lilin Carr, Antony M Liu, Cong |
| description | Double-strand breaks repaired by homologous recombination (HR) are first resected to form single-stranded DNA, which binds replication protein A (RPA). RPA attracts mediators that load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nucleosome-packaged DNA is poorly understood. Here we report that in Schizosaccharomyces pombe a conserved DDB1-CUL4-associated factor (DCAF), Wdr70, is recruited to DSBs as part of the Cullin4-DDB1 ubiquitin ligase (CRL4(Wdr70)) and stimulates distal H2B lysine 119 mono-ubiquitination (uH2B). Wdr70 deletion, or uH2B loss, results in increased loading of the checkpoint adaptor and resection inhibitor Crb2(53BP1), decreased Exo1 association and delayed resection. Wdr70 is dispensable for resection upon Crb2(53BP1) loss, or when the Set9 methyltransferase that creates docking sites for Crb2 is deleted. Finally, we establish that this histone regulatory cascade similarly controls DSB resection in human cells. |
| doi_str_mv | 10.1038/ncomms11364 |
| format | Article |
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Finally, we establish that this histone regulatory cascade similarly controls DSB resection in human cells.</description><subject>Amino Acid Sequence</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA, Single-Stranded - genetics</subject><subject>DNA, Single-Stranded - metabolism</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Exodeoxyribonucleases - genetics</subject><subject>Exodeoxyribonucleases - metabolism</subject><subject>HEK293 Cells</subject><subject>Histone-Lysine N-Methyltransferase - genetics</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Rad51 Recombinase - genetics</subject><subject>Rad51 Recombinase - metabolism</subject><subject>Recombinational DNA Repair</subject><subject>Replication Protein A - genetics</subject><subject>Replication Protein A - metabolism</subject><subject>Schizosaccharomyces - genetics</subject><subject>Schizosaccharomyces - metabolism</subject><subject>Schizosaccharomyces pombe Proteins - genetics</subject><subject>Schizosaccharomyces pombe Proteins - metabolism</subject><subject>Sequence Alignment</subject><subject>Signal Transduction</subject><subject>Ubiquitin-Protein Ligases - deficiency</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitination</subject><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kE1LxDAYhIMg7rLuybv0uB6qeZN02xx1WT9gQZAVjyUfbyXSJt0mBf33Vl3nMpdnBmYIuQB6DZRXN96ErosAfC1OyJxRATmUjM_IMsYPOolLqIQ4IzNWUlkJWc7J6-ZlJ1ZvdijpVTbg-9iqhDF7ZHdZF3wYtTuMLjmvkgs-U95mjTKudekX234GyC326C36NOUjmh_wnJw2qo24PPqC7O-3-81jvnt-eNrc7vKeAaQc6FpoWmkjixKLwjJGJS-FhUoWugEBkxhXCgutmaFoJXJFqbGyYVQjX5DVX20_hMOIMdWdiwbbVnkMY6yhrKbJIAWb0MsjOuoObd0PrlPDV_3_BP8GBeZeFw</recordid><startdate>20160421</startdate><enddate>20160421</enddate><creator>Zeng, Ming</creator><creator>Ren, Laifeng</creator><creator>Mizuno, Ken'Ichi</creator><creator>Nestoras, Konstantinos</creator><creator>Wang, Haibin</creator><creator>Tang, Zizhi</creator><creator>Guo, Liandi</creator><creator>Kong, Daochun</creator><creator>Hu, Qiwen</creator><creator>He, Qun</creator><creator>Du, Lilin</creator><creator>Carr, Antony M</creator><creator>Liu, Cong</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20160421</creationdate><title>CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection</title><author>Zeng, Ming ; Ren, Laifeng ; Mizuno, Ken'Ichi ; Nestoras, Konstantinos ; Wang, Haibin ; Tang, Zizhi ; Guo, Liandi ; Kong, Daochun ; Hu, Qiwen ; He, Qun ; Du, Lilin ; Carr, Antony M ; Liu, Cong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-1064b08bc957e55d2209374d1895bf14111123aae5bb2c0ed9e3a00cd9f20be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amino Acid Sequence</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA Breaks, Double-Stranded</topic><topic>DNA, Single-Stranded - genetics</topic><topic>DNA, Single-Stranded - metabolism</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Exodeoxyribonucleases - genetics</topic><topic>Exodeoxyribonucleases - metabolism</topic><topic>HEK293 Cells</topic><topic>Histone-Lysine N-Methyltransferase - genetics</topic><topic>Histone-Lysine N-Methyltransferase - metabolism</topic><topic>Humans</topic><topic>Molecular Sequence Data</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Rad51 Recombinase - genetics</topic><topic>Rad51 Recombinase - metabolism</topic><topic>Recombinational DNA Repair</topic><topic>Replication Protein A - genetics</topic><topic>Replication Protein A - metabolism</topic><topic>Schizosaccharomyces - genetics</topic><topic>Schizosaccharomyces - metabolism</topic><topic>Schizosaccharomyces pombe Proteins - genetics</topic><topic>Schizosaccharomyces pombe Proteins - metabolism</topic><topic>Sequence Alignment</topic><topic>Signal Transduction</topic><topic>Ubiquitin-Protein Ligases - deficiency</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeng, Ming</creatorcontrib><creatorcontrib>Ren, Laifeng</creatorcontrib><creatorcontrib>Mizuno, Ken'Ichi</creatorcontrib><creatorcontrib>Nestoras, Konstantinos</creatorcontrib><creatorcontrib>Wang, Haibin</creatorcontrib><creatorcontrib>Tang, Zizhi</creatorcontrib><creatorcontrib>Guo, Liandi</creatorcontrib><creatorcontrib>Kong, Daochun</creatorcontrib><creatorcontrib>Hu, Qiwen</creatorcontrib><creatorcontrib>He, Qun</creatorcontrib><creatorcontrib>Du, Lilin</creatorcontrib><creatorcontrib>Carr, Antony M</creatorcontrib><creatorcontrib>Liu, Cong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeng, Ming</au><au>Ren, Laifeng</au><au>Mizuno, Ken'Ichi</au><au>Nestoras, Konstantinos</au><au>Wang, Haibin</au><au>Tang, Zizhi</au><au>Guo, Liandi</au><au>Kong, Daochun</au><au>Hu, Qiwen</au><au>He, Qun</au><au>Du, Lilin</au><au>Carr, Antony M</au><au>Liu, Cong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection</atitle><jtitle>Nature communications</jtitle><addtitle>Nat Commun</addtitle><date>2016-04-21</date><risdate>2016</risdate><volume>7</volume><spage>11364</spage><epage>11364</epage><pages>11364-11364</pages><eissn>2041-1723</eissn><abstract>Double-strand breaks repaired by homologous recombination (HR) are first resected to form single-stranded DNA, which binds replication protein A (RPA). RPA attracts mediators that load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nucleosome-packaged DNA is poorly understood. Here we report that in Schizosaccharomyces pombe a conserved DDB1-CUL4-associated factor (DCAF), Wdr70, is recruited to DSBs as part of the Cullin4-DDB1 ubiquitin ligase (CRL4(Wdr70)) and stimulates distal H2B lysine 119 mono-ubiquitination (uH2B). Wdr70 deletion, or uH2B loss, results in increased loading of the checkpoint adaptor and resection inhibitor Crb2(53BP1), decreased Exo1 association and delayed resection. Wdr70 is dispensable for resection upon Crb2(53BP1) loss, or when the Set9 methyltransferase that creates docking sites for Crb2 is deleted. 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| subjects | Amino Acid Sequence Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism DNA - genetics DNA - metabolism DNA Breaks, Double-Stranded DNA, Single-Stranded - genetics DNA, Single-Stranded - metabolism DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Exodeoxyribonucleases - genetics Exodeoxyribonucleases - metabolism HEK293 Cells Histone-Lysine N-Methyltransferase - genetics Histone-Lysine N-Methyltransferase - metabolism Humans Molecular Sequence Data Nuclear Proteins - genetics Nuclear Proteins - metabolism Rad51 Recombinase - genetics Rad51 Recombinase - metabolism Recombinational DNA Repair Replication Protein A - genetics Replication Protein A - metabolism Schizosaccharomyces - genetics Schizosaccharomyces - metabolism Schizosaccharomyces pombe Proteins - genetics Schizosaccharomyces pombe Proteins - metabolism Sequence Alignment Signal Transduction Ubiquitin-Protein Ligases - deficiency Ubiquitin-Protein Ligases - genetics Ubiquitination |
| title | CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection |
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