Evidence map›Paper›PMID 27871366›Full record

ArticleMolecular cell2016

Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair.

Bruno Vaz, Marta Popovic, Joseph A Newman, John Fielden, Hazel Aitkenhead, Swagata Halder, Abhay Narayan Singh, Iolanda Vendrell, Roman Fischer, Ignacio Torrecilla and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.

0numbers the graph read from it
0cells of the map it votes in
156citing papers in PubMed
13.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

156 citing papers in PubMed, 247 citations in OpenAlex.

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  15. Role of TDP2 in the repair of DNA damage induced by the radiomimetic drug Bleomycin.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025
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  18. Mechanisms of DNA repair and mutagenesis induced by acetaldehyde, acrolein, aristolochic acids, and vinyl chloride.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025
    Review
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96 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 3 countries.

Bruno VazCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Marta PopovicCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Joseph A NewmanStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.
John FieldenCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Hazel AitkenheadStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.
Swagata HalderCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Abhay Narayan SinghCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Iolanda VendrellCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK; TDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Roman FischerTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Ignacio TorrecillaCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Neele DrobnitzkyCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Raimundo FreireUnidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, Ofra s/n, 38320 La Laguna, Tenerife, Spain.
David J AmorBruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Paul J LockhartBruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Benedikt M KesslerTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Gillies W McKennaCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Opher GileadiStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.
Kristijan RamadanCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: kristijan.ramadan@oncology.ox.ac.uk.
University of Oxford · GBMedical Research Council · GBCancer Research UK · GBGenomics (United Kingdom) · GBHospital Universitario de Canarias · ESMurdoch Children's Research Institute · AURoyal Children's Hospital · AU

Funding

Medical Research Council MC_PC_12001/1Wellcome Trust 097813/Z/11/ZWellcome Trust 106169/ZZ14/Z
6 · The paper itself

Abstract

The cytotoxicity of DNA-protein crosslinks (DPCs) is largely ascribed to their ability to block the progression of DNA replication. DPCs frequently occur in cells, either as a consequence of metabolism or exogenous agents, but the mechanism of DPC repair is not completely understood. Here, we characterize SPRTN as a specialized DNA-dependent and DNA replication-coupled metalloprotease for DPC repair. SPRTN cleaves various DNA binding substrates during S-phase progression and thus protects proliferative cells from DPC toxicity. Ruijs-Aalfs syndrome (RJALS) patient cells with monogenic and biallelic mutations in SPRTN are hypersensitive to DPC-inducing agents due to a defect in DNA replication fork progression and the inability to eliminate DPCs. We propose that SPRTN protease represents a specialized DNA replication-coupled DPC repair pathway essential for DNA replication progression and genome stability. Defective SPRTN-dependent clearance of DPCs is the molecular mechanism underlying RJALS, and DPCs are contributing to accelerated aging and cancer.

Indexed as

DNA RepairDNA ReplicationGenomic InstabilityAmino Acid SequenceBinding SitesCross-Linking ReagentsDNADNA-Binding ProteinsDNA DamageEtoposideFormaldehydeGene ExpressionHumansKineticsMutationProtein BindingCross-Linking ReagentsDNADNA-Binding ProteinsEtoposideFormaldehydeSPRTN protein, humanagingcancerDNA-dependent metalloproteaseDNA-protein crosslink repairDNA replicationRuijs-Aalfs/SPARTAN syndromeSPARTAN/DVC1

Identifiers

PMID27871366
PMCPMC5128727
OpenAlexW2543333792

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.