Proteomics

Dataset Information

0

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


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Arminja Kettenbach  

PROVIDER: MSV000087884 | MassIVE | Mon Jul 26 13:15:00 BST 2021

SECONDARY ACCESSION(S): PXD027574

REPOSITORIES: MassIVE

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-03-11 | PXD030297 | Pride
2019-05-16 | MSV000083785 | MassIVE
2021-03-04 | MSV000087003 | MassIVE
2019-08-28 | MSV000084245 | MassIVE
2020-12-07 | PXD022755 | Pride
2021-06-11 | MSV000087616 | MassIVE
2017-05-14 | GSE95801 | GEO
2018-11-28 | GSE116017 | GEO
2019-07-31 | PXD012486 | Pride
| 116295 | ecrin-mdr-crc