PXD043107-2

PXD043107 is an original dataset announced via ProteomeXchange.

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

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.

10.1038/S41467-024-50912-X;

submitter keyword: Xenopus, PARP1, TOP1, DNA-protein crosslink, ADP-ribosylation, DDI2, DNA damage, ubiquitin, SUMO, p97

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD043107

PRIDE project URI

• PRIDE
  1. PXD043107
     1. Label: PRIDE project
     2. Name: PARP1-dependent DNA-protein crosslink repair