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PXD043522

PXD043522 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity
DescriptionRecent studies have highlighted the critical role of metabolism in the response to DNA damage. However, the precise metabolic interactions that are set in motion to tune this fundamental process remain largely unknown. In this study, we investigated the role of nuclear metabolism in the DNA damage response using triple-negative breast cancer as a model. By comparing the chromatin-associated proteome of different breast cancer subtypes, we observed that the purine synthesis enzyme Inosine monophosphate dehydrogenase 2 (IMPDH2) is enriched in the chromatin of triple-negative breast cancer cells, which are often prone to DNA damage accumulation. Downregulation, depletion, or inhibition of IMPDH2 leads to accumulation of DNA damage. IMPDH2 chromatin localization is DNA damage dose dependent and happens at a late stage of the DNA damage repair. On chromatin, IMPDH2 interacts with PARP1. The enzymatic function of IMPDH2, which consumes NAD+, modulates PARP1 activity, thus mediating a pondered DNA damage response. However, forcing the nuclear localization of exogenous IMPDH2 provokes a dramatic NAD+ depletion that results in PARP1 cleavage and consequent cytoplasmic translocation, which mediates apoptosis. Our study identifies a moonlighting role for IMPDH2 in the control of nuclear ATP and NAD+ level, which fine-tune the activation of PARP1 and regulates the DNA damage response.
HostingRepositoryPRIDE
AnnounceDate2024-11-28
AnnouncementXMLSubmission_2024-11-28_05:35:58.052.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEduard Sabidó
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-04 01:35:05ID requested
12024-11-28 05:35:58announced
Publication List
10.1038/S41467-024-53877-Z;
Keyword List
submitter keyword: proteomics,PARP1, IMPDH2, DNA damage
Contact List
Eduard Sabidó
contact affiliationCentre for Genomic Regulation
contact emaileduard.sabido@crg.cat
lab head
Eduard Sabidó
contact affiliationCentre de Regulació Genòmica
contact emaileduard.sabido@crg.cat
dataset submitter
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Dataset FTP location
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