PXD004154

PXD004154 is an original dataset announced via ProteomeXchange.

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	2017-10-24
AnnouncementXML	Submission_2017-10-24_01:47:44.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

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.

Vaz B, Popovic M, Newman JA, Fielden J, Aitkenhead H, Halder S, Singh AN, Vendrell I, Fischer R, Torrecilla I, Drobnitzky N, Freire R, Amor DJ, Lockhart PJ, Kessler BM, McKenna GW, Gileadi O, Ramadan K, Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair. Mol Cell, 64(4):704-719(2016) [pubmed]

curator keyword: Biological

submitter keyword: DNA-Protein Crosslink

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

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/2016/10/PXD004154

PRIDE project URI

• PRIDE
  1. PXD004154
     1. Label: PRIDE project
     2. Name: Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Removal