PXD043522 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity |
Description | Recent 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-11-28 |
AnnouncementXML | Submission_2024-11-28_05:35:58.052.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Eduard Sabidó |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-07-04 01:35:05 | ID requested | |
⏵ 1 | 2024-11-28 05:35:58 | announced | |
Publication List
Keyword List
submitter keyword: proteomics,PARP1, IMPDH2, DNA damage |
Contact List
Eduard Sabidó |
contact affiliation | Centre for Genomic Regulation |
contact email | eduard.sabido@crg.cat |
lab head | |
Eduard Sabidó |
contact affiliation | Centre de Regulació Genòmica |
contact email | eduard.sabido@crg.cat |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043522
- Label: PRIDE project
- Name: Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity