PXD009040 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A SUMO-mediated protective response to DNA-protein crosslinks |
Description | DNA-protein crosslinks (DPCs) are highly cytotoxic lesions that obstruct essential DNA transactions and whose resolution is critical for cell and organismal fitness. However, unlike the repair pathways for most types of DNA damage, the mechanisms by which cells respond to and overcome DPCs remain poorly understood. Recent studies unveiled a dedicated DPC repair pathway in higher eukaryotes involving the SprT-type metalloprotease SPRTN/DVC1, which proteolytically processes DPCs during DNA replication in a ubiquitin-controlled manner. Here, we show that aldehyde-generated DPCs elicit a potent and highly dynamic, cell cycle-independent SUMOylation response impacting numerous chromatin-associated human proteins. We identify an uncharacterized SprT metalloprotease, ACRC, which unlike SPRTN is targeted to DPCs in a SUMO-dependent manner. Moreover, we establish important physiological roles of the C. elegans ACRC orthologue GCNA-1 and SUMO-mediated signaling in promoting organismal survival upon DPC formation. Finally, we demonstrate that like aldehydes, defined enzymatic DNMT1 DPCs trigger a robust SUMO response targeting the crosslinked proteins and associated factors to promote efficient lesion processing and cellular fitness. Collectively, our findings reveal an evolutionarily conserved general role of SUMO-mediated signaling in facilitating responses to DPCs in metazoans. |
HostingRepository | PRIDE |
AnnounceDate | 2019-03-26 |
AnnouncementXML | Submission_2019-03-28_13:46:33.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Ivo Hendriks |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | sumoylated lysine |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-02-26 07:08:24 | ID requested | |
1 | 2019-03-26 08:27:47 | announced | |
⏵ 2 | 2019-03-28 13:46:34 | announced | Updated publication reference for PubMed record(s): 30914427. |
Publication List
Borgermann N, Ackermann L, Schwertman P, Hendriks IA, Thijssen K, Liu JC, Lans H, Nielsen ML, Mailand N, SUMOylation promotes protective responses to DNA-protein crosslinks. EMBO J, 38(8):(2019) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: SUMO, ubquitin, DNMT1, DNA-protein crosslink, DNA damage, DNA repair, human, Q Exactive HF, Q Exactive HF-X |
Contact List
Michael Lund Nielsen |
contact affiliation | 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009040
- Label: PRIDE project
- Name: A SUMO-mediated protective response to DNA-protein crosslinks