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PXD039228

PXD039228 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleD-type cyclins determine the activity of DNA mismatch repair in the G1 and S phases of the cell cycle
DescriptionThe large majority of oxidative lesions occurring in the G1 phase of the cell cycle are repaired by base excision repair (BER) rather than mismatch repair (MMR) to avoid long resections that can lead to genomic instability and cell death. However, how cells choose BER over MMR is not yet understood. Here, we show that, during G1, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. In turn, in a manner that is independent on CDK4/6 activity, D-type cyclins stabilize p21, which competes through its PCNA-interacting protein (PIP) box with MMR components for their binding to PCNA. This reduces MMR activity while allowing BER. At the G1/S transition, the AMBRA1-dependent degradation of D-type cyclins renders p21 susceptible to proteolysis via SKP2 and CDT2. These timely degradation events allow the proper binding of MMR proteins to PCNA enabling the repair of DNA replication errors. Thus, the expression of D-type cyclins limit MMR in G1, whereas their degradation is necessary for proper MMR function in S. Defects in these two regulatory mechanisms promote genome instability. The mass spectrometry raw files correspond to the affinity purifications of proximity labeled (turbo-ID) PCNA and CCND1 under various conditions.
HostingRepositoryMassIVE
AnnounceDate2024-02-05
AnnouncementXMLSubmission_2024-02-05_12:52:43.836.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBeatrix Ueberheide
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListOxidation; Deamidated
InstrumentQ Exactive; Q Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-01-03 14:48:46ID requested
12024-02-05 12:52:44announced
Publication List
no publication
Keyword List
submitter keyword: proximity labeling, turbo-ID, PCNA, CCND1, D-type cyclins, DNA mismatch repair
Contact List
Beatrix Ueberheide
contact affiliationNYU Grossman School of Medicine
contact emailbeatrix.ueberheide@nyulangone.org
lab head
Beatrix Ueberheide
contact affiliationNYU School of Medicine
contact emailbeatrixueberheide@gmail.com
dataset submitter
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MassIVE dataset URI
Dataset FTP location
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