PXD043107 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | PARP1-dependent DNA-protein crosslink repair |
Description | DNA-protein crosslinks (DPCs) are toxic lesions that inhibit DNA related processes. Post-translational modifications (PTMs), including SUMOylation and ubiquitylation, play a central role in DPC resolution, but whether other PTMs are also involved remains elusive. Here, we identify a DPC repair pathway orchestrated by poly-ADP-ribosylation (PARylation). Using Xenopus egg extracts, we show that DPCs on single-stranded DNA gaps can be targeted for degradation via a replication-independent mechanism. During this process, DPCs are initially PARylated by PARP1 and subsequently ubiquitylated and degraded by the proteasome. Notably, PARP1-mediated DPC resolution is required for resolving topoisomerase 1-DNA cleavage complexes (TOP1ccs) induced by camptothecin. Using the Flp-nick system, we further reveal that in the absence of PARP1 activity, the TOP1cc-like lesion persists and induces replisome disassembly when encountered by a DNA replication fork. In summary, our work uncovers a PARP1-mediated DPC repair pathway that may underlie the synergistic toxicity between TOP1 poisons and PARP inhibitors. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:52:39.234.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Ivo Hendriks |
SpeciesList | scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-06-19 11:46:13 | ID requested | |
1 | 2024-08-06 01:45:58 | announced | |
⏵ 2 | 2024-10-22 06:52:39 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
submitter keyword: Xenopus, PARP1, TOP1, DNA-protein crosslink, ADP-ribosylation, DDI2, DNA damage, ubiquitin, SUMO, p97 |
Contact List
Ivo Hendriks |
contact affiliation | Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark |
contact email | ivo.a.hendriks@gmail.com |
lab head | |
Ivo Hendriks |
contact affiliation | Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark |
contact email | ivo.a.hendriks@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043107
- Label: PRIDE project
- Name: PARP1-dependent DNA-protein crosslink repair