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PXD050319

PXD050319 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleBRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis.
DescriptionDeficiencies in the BRCA1 tumor suppressor gene are the main cause of hereditary breast and ovarian cancer. BRCA1 is involved in the Homologous Recombination DNA repair pathway, and, together with BARD1, forms a heterodimer with ubiquitin E3 activity. The relevance of the BRCA1/BARD1 ubiquitin E3 activity for tumor suppression and DNA repair remains controversial and most efforts aimed to identify BRCA1/BARD1 ubiquitination substrates rely on indirect evidence. Here, we observed that the BRCA1/BARD1 ubiquitin E3 activity was not required for Homologous Recombination or resistance to Olaparib. Using TULIP2 methodology, which enables the direct identification of E3-specific ubiquitination substrates, we identified substrates for BRCA1/BARD1. We found that PCNA is ubiquitinated by BRCA1/BARD1 in unperturbed conditions independently of RAD18. PCNA ubiquitination by BRCA1/BARD1 avoids the formation of ssDNA gaps during DNA replication and promotes continuous DNA synthesis. These results address the controversy about the function of BRCA1/BARD1 E3 activity in Homologous Recombination.
HostingRepositoryPRIDE
AnnounceDate2024-05-08
AnnouncementXMLSubmission_2024-05-07_16:23:03.284.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRomán González-Prieto
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF SCP
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-04 04:13:55ID requested
12024-05-07 16:23:03announced
Publication List
10.1038/S41467-024-48427-6;
Keyword List
submitter keyword: ssDNA gaps, ubiquitination,BRCA1, BARD1, PCNA
Contact List
Román González Prieto
contact affiliationCABIMER - University of Sevilla
contact emailroman.gonzalez@cabimer.es
lab head
Román González-Prieto
contact affiliationAndalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact emailroman.gonzalez@cabimer.es
dataset submitter
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Dataset FTP location
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