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A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination

A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination

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AMBJØRN, Sara M., Julien P. DUXIN, Emil P. T. HERTZ, Isha NASA, Joana DURO, Thomas KRUSE, Beata RYMARCZYK, Vibe H. OESTERGAARD, Michael LISBY, Jakob NILSSON, 2021. A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination. In: Nature Communications. Nature Publishing Group. 12(1), 5748. eISSN 2041-1723. Available under: doi: 10.1038/s41467-021-26079-0

@article{Ambjrn2021-09-30compl-55702, title={A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination}, year={2021}, doi={10.1038/s41467-021-26079-0}, number={1}, volume={12}, journal={Nature Communications}, author={Ambjørn, Sara M. and Duxin, Julien P. and Hertz, Emil P. T. and Nasa, Isha and Duro, Joana and Kruse, Thomas and Rymarczyk, Beata and Oestergaard, Vibe H. and Lisby, Michael and Nilsson, Jakob}, note={Article Number: 5748} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/55702"> <dc:creator>Oestergaard, Vibe H.</dc:creator> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/55702/1/Ambj%c3%b8rn_2-hkyuu4qxxvbu6.pdf"/> <dc:creator>Duro, Joana</dc:creator> <dcterms:title>A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination</dcterms:title> <dc:contributor>Ambjørn, Sara M.</dc:contributor> <dc:contributor>Nasa, Isha</dc:contributor> <dc:creator>Nasa, Isha</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>Rymarczyk, Beata</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-11-29T15:24:15Z</dc:date> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <dcterms:issued>2021-09-30</dcterms:issued> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/55702/1/Ambj%c3%b8rn_2-hkyuu4qxxvbu6.pdf"/> <dc:creator>Ambjørn, Sara M.</dc:creator> <dcterms:abstract xml:lang="eng">Mutations in the tumour suppressor gene BRCA2 are associated with predisposition to breast and ovarian cancers. BRCA2 has a central role in maintaining genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination (HR). BRCA2 acts by controlling RAD51 nucleoprotein filament formation on resected single-stranded DNA, but how BRCA2 activity is regulated during HR is not fully understood. Here, we delineate a pathway where ATM and ATR kinases phosphorylate a highly conserved region in BRCA2 in response to DSBs. These phosphorylations stimulate the binding of the protein phosphatase PP2A-B56 to BRCA2 through a conserved binding motif. We show that the phosphorylation-dependent formation of the BRCA2-PP2A-B56 complex is required for efficient RAD51 filament formation at sites of DNA damage and HR-mediated DNA repair. Moreover, we find that several cancer-associated mutations in BRCA2 deregulate the BRCA2-PP2A-B56 interaction and sensitize cells to PARP inhibition. Collectively, our work uncovers PP2A-B56 as a positive regulator of BRCA2 function in HR with clinical implications for BRCA2 and PP2A-B56 mutated cancers.</dcterms:abstract> <dc:contributor>Duxin, Julien P.</dc:contributor> <dc:rights>Attribution 4.0 International</dc:rights> <dc:creator>Lisby, Michael</dc:creator> <dc:creator>Rymarczyk, Beata</dc:creator> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/55702"/> <dc:creator>Duxin, Julien P.</dc:creator> <dc:creator>Hertz, Emil P. T.</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:language>eng</dc:language> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-11-29T15:24:15Z</dcterms:available> <dc:contributor>Nilsson, Jakob</dc:contributor> <dc:contributor>Duro, Joana</dc:contributor> <dc:contributor>Oestergaard, Vibe H.</dc:contributor> <dc:contributor>Kruse, Thomas</dc:contributor> <dc:creator>Nilsson, Jakob</dc:creator> <dc:contributor>Hertz, Emil P. T.</dc:contributor> <dc:contributor>Lisby, Michael</dc:contributor> <dc:creator>Kruse, Thomas</dc:creator> </rdf:Description> </rdf:RDF>

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