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PXD043107-1

PXD043107 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePARP1-dependent DNA-protein crosslink repair
DescriptionDNA-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.
HostingRepositoryPRIDE
AnnounceDate2024-08-06
AnnouncementXMLSubmission_2024-08-06_01:45:58.047.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterIvo Hendriks
SpeciesList scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-06-19 11:46:13ID requested
12024-08-06 01:45:58announced
22024-10-22 06:52:39announced2024-10-22: Updated project metadata.
Publication List
10.1038/S41467-024-50912-X;
Keyword List
submitter keyword: Xenopus, PARP1, TOP1, DNA-protein crosslink, ADP-ribosylation, DDI2, DNA damage, ubiquitin, SUMO, p97
Contact List
Ivo Hendriks
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailivo.a.hendriks@gmail.com
lab head
Ivo Hendriks
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailivo.a.hendriks@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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