PXD004154 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Removal |
Description | Cytotoxicity of DNA-protein crosslinks (DPCs) is ascribed largely to their ability to block the progression of DNA replication fork. DPCs are frequently occurring in cells, either as a consequence of metabolism or exogenous agents. The mechanism of DPCs removal is not completely understood. Here, we characterize SPRTN (DVC1) as specialised DNA-dependent metalloprotease for DPC removal in humans. SPRTN has an N-terminal metalloprotease domain that cleaves various DNA binding substrate during S-phase progression. SPRTN is a part of replisome and removes DPCs during DNA replication fork progression, thus protecting proliferative cells from DPCs toxicity. Ruijs-Aalfs Syndrome (RJALS) patient cells with monogenic mutations in SPRTN are hypersensitive to DPC-inducing agents due to DPC removal defect and DNA replication fork stalling. We propose a model where SPRTN protease forms specialised DNA-replication coupled DPC removal pathway essential for DNA replication fork progression and genome stability. We conclude RJALS is the first human syndrome linked to this pathway |
HostingRepository | PRIDE |
AnnounceDate | 2016-10-06 |
AnnouncementXML | Submission_2016-10-06_07:58:23.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD004154 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Roman Fischer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | Oxidation; Oxidation |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-05-16 01:54:58 | ID requested | |
⏵ 1 | 2016-10-06 07:58:23 | announced | |
2 | 2016-12-09 05:00:42 | announced | Updated publication reference for PubMed record(s): 27871366. |
3 | 2017-10-24 01:47:46 | announced | Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
curator keyword: Biological |
submitter keyword: DNA-Protein Crosslink |
Contact List
Roman Fischer |
contact affiliation | Target Discovery Institute, University of Oxford, UK |
contact email | roman.fischer@ndm.ox.ac.uk |
lab head | |
Roman Fischer |
contact affiliation | University of Oxford |
contact email | roman.fischer@ndm.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD004154
- Label: PRIDE project
- Name: Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Removal