PXD021947-1

PXD021947 is an original dataset announced via ProteomeXchange.

Title	Mechanism and function of DNA replication-independent DNA-protein crosslink repair via the SUMO pathway
Description	DNA-protein crosslinks (DPCs) obstruct essential DNA transactions, posing a serious threat to genome stability and functionality. DPCs are proteolytically processed in a ubiquitin- and DNA replication-dependent manner by SPRTN or the proteasome but can also be resolved via targeted SUMOylation. However, the mechanistic basis of SUMO-mediated DPC resolution and its interplay with replication-coupled DPC repair pathways remain unknown. Here, we show that the SUMO-targeted ubiquitin ligase RNF4 defines a major pathway for ubiquitylation and proteasomal clearance of SUMOylated DPCs in a DNA replication-independent manner. In addition, we provide evidence that a subset of DPCs can be SUMOylated and processed via transcription, independently of RNF4. SUMO modification of DPCs is mediated by PIAS4 and neither stimulates nor inhibits their rapid DNA replication-dependent proteolysis. Instead, SUMOylation provides a critical salvage mechanism to remove DPCs formed or persisting after replication, as we demonstrate that DPCs on duplex DNA do not activate interphase DNA damage checkpoints. Consequently, in the absence of the SUMO-RNF4 pathway cells can enter mitosis with a high load of unresolved DPCs, leading to defective chromosome segregation and cell death. Collectively, these findings provide mechanistic insights into SUMO-driven pathways underlying replication-independent DPC resolution and highlight their critical importance in maintaining chromosome stability and cellular fitness.
HostingRepository	PRIDE
AnnounceDate	2021-08-06
AnnouncementXML	Submission_2021-08-06_01:42:32.044.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	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-13 02:48:55	ID requested
⏵ 1	2021-08-06 01:42:32	announced
2	2023-11-14 08:51:40	announced	2023-11-14: Updated project metadata.

10.15252/EMBJ.2020107413;

submitter keyword: CHROMASS, Xenopus, DNA damage, replication, DPC, SUMO, RNF4, PIAS4

Michael Lund Nielsen
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	michael.lund.nielsen@cpr.ku.dk
lab head
Ivo Hendriks
contact affiliation	Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
contact email	ivo.a.hendriks@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021947
     1. Label: PRIDE project
     2. Name: Mechanism and function of DNA replication-independent DNA-protein crosslink repair via the SUMO pathway