PXD040676 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | PDHE1α, PARylation, Acetyl-CoA, Acetylation, Histones, DNA damage repair |
Description | Chromatin relaxation is a prerequisite step that allows the DNA repair machinery to access double-strand breaks (DSBs), and local histones around the DNA breaks suffer from prompt acetylation changes. However, an intriguing question remains as to where the large demands of acetyl-CoA is precisely produced promptly. Here, we report that pyruvate dehydrogenase 1α (PDHE1α) catalyzes pyruvate metabolism to provide acetyl-CoA promptly in response to DNA damage. PDHE1α was quickly recruited to chromatin in a PARylation-dependent manner, which further drove acetyl-CoA generation to support local chromatin acetylation around the DSB regions. In turn, this process increased the formation of relaxed chromatin to benefit repair factor loading, thus promoting DSB repair to ultimately maintain genome stability and contribute to the resistance of cancer cells to DNA-damaging treatments in vitro and in vivo. In accordance with this, blocking PARylation-based PDHE1α chromatin recruitment markedly attenuated chromatin relaxation and the DSB repair efficiency, resulting in genome instability and restoration of radiosensitivity. Collectively, these findings reveal an undescribed mechanism that underlies site-directed acetyl-CoA generation involving chromatin-associated PDHE1α and its instrumental function in DNA repair and regulating local chromatin acetylation around DSB sites. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:58:12.428.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jun Zhang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-03-07 20:12:04 | ID requested | |
1 | 2023-07-26 18:50:11 | announced | |
⏵ 2 | 2024-10-22 05:58:12 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: PDHE1α, Acetyl-CoA, DNA damage repair, PARylation, Histones, Acetylation |
Contact List
Jun Zhang |
contact affiliation | junzh128@szu.edu.cn |
contact email | junzh128@szu.edu.cn |
lab head | |
Jun Zhang |
contact affiliation | Shenzhen University |
contact email | junzh128@szu.edu.cn |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD040676
- Label: PRIDE project
- Name: PDHE1α, PARylation, Acetyl-CoA, Acetylation, Histones, DNA damage repair