PXD027574-1
PXD027574 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A complex of BRCA2 and PP2A-B56 is required for homologous recombination-mediated DNA repair |
| Description | Mutations in the tumour suppressor BRCA2 are associated with predisposition to breast and ovarian cancers. BRCA2 has a central role in genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination. BRCA2 acts by promoting RAD51 nucleofilament 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 DNA 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 loading to 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2021-09-03 |
| AnnouncementXML | Submission_2021-09-03_08:12:51.674.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Mark Adamo |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl; Phospho |
| Instrument | Orbitrap Fusion Lumos; Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-07-26 13:15:57 | ID requested | |
| ⏵ 1 | 2021-09-03 08:12:52 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: BRCA2, cancer, breast, ovarian, DSB, homologous recombination, RAD51, HR, ATM, ATR, kinase, PP2A-B56, PARP |
Contact List
| Arminja Kettenbach | |
|---|---|
| contact affiliation | The Geisel School of Medicine at Dartmouth |
| contact email | arminja.n.kettenbach@dartmouth.edu |
| lab head | |
| Mark Adamo | |
| contact affiliation | Dartmouth College |
| contact email | mark.e.adamo@dartmouth.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000087884/ |
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