{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360286994890920832.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1101/776823"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1101/776823"}}],"resourceType":"preprint","dc:title":[{"@value":"A novel nuclear speckle factor, USP42, promotes homologous recombination repair by resolving DNA double-strand break induced R-loop"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                <jats:p>The nucleus of mammalian cells is highly compartmentalized by nuclear bodies, including nuclear speckles. While nuclear bodies are known to function in regulating gene expression, their involvement in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, revealed that nuclear speckle factors regulating transcription are potentially involved in the regulation of HR. Among the top hits, we provide evidence showing that USP42, which is a deubiquitylating enzyme and a hitherto unidentified nuclear speckles factor, promotes HR by facilitating BRCA1 recruitment to DSB sites and DNA-end resection. We further showed that USP42 localizes to nuclear speckles via an intrinsically disordered region, which is required for efficient HR. Furthermore, we established that USP42 interacts with DHX9, which possesses DNA-RNA helicase activity, and is required for efficient resolution of DSB-induced R-loop. Mechanistically, USP42 antagonizes mono-ubiquitylation of DHX9 that is evoked after DSB induction. In conclusion, our data propose a model in which a novel nuclear speckle factor, USP42, facilitates DSB-induced R-loop resolution, BRCA1 loading to DSB sites and preferential DSB repair by HR, indicating the importance of spatial regulation of DSB repair choice mediated by nuclear bodies.</jats:p>\n                <jats:sec>\n                  <jats:title>Significant statement</jats:title>\n                  <jats:p>Defects in the repair of DNA double-strand break (DSB), which is one of the most harmful DNA insults, cause human diseases including cancers. It has been suggested that DSBs generated in the coding region tend to be repaired by homologous recombination (HR) that is error-free DSB repair pathway. To reveal the spatial regulation of HR, in this study, we investigated the potential contribution of nuclear bodies, especially nuclear speckles, to HR, identifying a deubiquitylating enzyme USP42 as a HR promoting factor. We found that USP42 deubiquitylates DHX9, facilitates resolution of DNA-RNA hybrid structure and enhances HR through BRCA1 loading to DSB sites.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Classification</jats:title>\n                  <jats:p>Biological Sciences, Cell Biology</jats:p>\n                </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380286994890920835","@type":"Researcher","foaf:name":[{"@value":"Misaki Matsui"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890920833","@type":"Researcher","foaf:name":[{"@value":"Ryo Sakasai"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890921090","@type":"Researcher","foaf:name":[{"@value":"Masako Abe"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890920834","@type":"Researcher","foaf:name":[{"@value":"Yusuke Kimura"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890920962","@type":"Researcher","foaf:name":[{"@value":"Shoki Kajita"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890920961","@type":"Researcher","foaf:name":[{"@value":"Wakana Torii"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890921088","@type":"Researcher","foaf:name":[{"@value":"Yoko Katsuki"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890920836","@type":"Researcher","foaf:name":[{"@value":"Masamichi Ishiai"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890920960","@type":"Researcher","foaf:name":[{"@value":"Kuniyoshi Iwabuchi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380286994890920832","@type":"Researcher","foaf:name":[{"@value":"Minoru Takata"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801201773952","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"80446525"},{"@type":"NRID","@value":"1000080446525"},{"@type":"NRID","@value":"9000297499385"},{"@type":"NRID","@value":"9000329440440"},{"@type":"NRID","@value":"9000010250537"},{"@type":"NRID","@value":"9000297499379"},{"@type":"NRID","@value":"9000380434032"},{"@type":"NRID","@value":"9000297499396"},{"@type":"NRID","@value":"9000024998104"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0107554"}],"foaf:name":[{"@value":"Ryotaro Nishi"}]}],"publication":{"dc:publisher":[{"@value":"openRxiv"}],"prism:publicationDate":"2019-09-20"},"reviewed":"false","url":[{"@id":"https://syndication.highwire.org/content/doi/10.1101/776823"}],"createdAt":"2019-09-20","modifiedAt":"2026-01-14","project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256878751744","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"16H05888"},{"@type":"JGN","@value":"JP16H05888"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16H05888/"}],"notation":[{"@language":"ja","@value":"核内構造体によるDNA二重鎖切断修復制御機構の解明"},{"@language":"en","@value":"DNA double-strand break repair regulated by nuclear bodies"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004232043621376","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination 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