ArticleNature genetics2014
Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features.
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Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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141citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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141 citing papers in PubMed, 241 citations in OpenAlex.
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- ACRC/GCNA is an essential protease that repairs DNA-protein crosslinks during vertebrate development.Nucleic acids research · 2026Article
- A manually curated gene-phenotype catalogue for progeroid syndromes and premature aging.Aging · 2026Article
- Living Cells Employ Ubiquitin-Proteasomal System and Nucleotide Excision Repair Pathways to Remove Reactive Oxygen Species-Induced DNA-Protein Crosslinks (ROS-DPCs).bioRxiv : the preprint server for biology · 2026Article
- Signatures of high-altitude adaptation in Caucasus populations: evidence from the EGLN1-SPRTN locus.Genetica · 2026Article
- Long-Patch Base Excision Repair of 5'-DNA-Peptide Cross-Links Derived from Abasic DNA Lesions.Biochemistry · 2026Article
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
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- Lipodystrophy Syndromes: One Name but Many Diseases Highlighting the Importance of Adipose Tissue in Metabolism.Current diabetes reports · 2025Review
- Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability.Nature communications · 2025Article
- The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks.Nucleic acids research · 2025Article
- DNA-Protein Cross-Links Derived from Abasic DNA Lesions: Recent Progress and Future Directions.Chemical research in toxicology · 2025Review
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- Electro-elution-based purification of covalent DNA-protein cross-links.Nature protocols · 2024Review
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
- Endogenous Cellular Metabolite Methylglyoxal Induces DNA-Protein Cross-Links in Living Cells.ACS chemical biology · 2024Article
81 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 15 institutions in 8 countries.
Davor Lessel1] Institute of Human Genetics, University of Ulm, Ulm, Germany. [2] Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Bruno VazCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK.
Swagata Halder1] Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK. [2] Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Zürich, Switzerland.
Paul J Lockhart1] Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia. [2] Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.ORCID 0000000325318413
Ivana Marinovic-TerzicDepartment of Immunology and Medical Genetics, University of Split, School of Medicine, Split, Croatia.
Jaime Lopez-Mosqueda1] Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt (Main), Germany. [2] Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt (Main), Germany.
Melanie PhilippDepartment of Biochemistry and Molecular Biology, University of Ulm, Ulm, Germany.
Joe C H SimBruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
Katherine R Smith1] Bioinformatics Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia. [2] Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.ORCID 0000000203295938
Judith Oehler1] Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK. [2] Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Zürich, Switzerland.
Elisa CabreraUnidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, La Laguna, Tenerife, Spain.
Raimundo FreireUnidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, La Laguna, Tenerife, Spain.
Kate PopeBruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
Amsha NahidBioinformatics Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia.
Fiona NorrisVictorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
Richard J Leventer1] Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. [2] Neuroscience Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. [3] Department of Neurology, Royal Children's Hospital, Parkville, Victoria, Australia.
Martin B Delatycki1] Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia. [2] Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia. [3] Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia.
Gotthold BarbiInstitute of Human Genetics, University of Ulm, Ulm, Germany.
Simon von AmelnInstitute of Human Genetics, University of Ulm, Ulm, Germany.
Josef HögelInstitute of Human Genetics, University of Ulm, Ulm, Germany.
Marina DegoricijaDepartment of Immunology and Medical Genetics, University of Split, School of Medicine, Split, Croatia.
Regina FertigInstitute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Zürich, Switzerland.
Martin D BurkhalterLeibniz Institute for Age Research, Fritz Lippmann Institute, Jena, Germany.
Kay HofmannInstitute of Genetics, University of Cologne, Cologne, Germany.ORCID 0000000222899083
Holger ThieleCologne Center for Genomics, University of Cologne, Cologne, Germany.
Janine AltmüllerCologne Center for Genomics, University of Cologne, Cologne, Germany.
Gudrun NürnbergCologne Center for Genomics, University of Cologne, Cologne, Germany.
Peter Nürnberg1] Cologne Center for Genomics, University of Cologne, Cologne, Germany. [2] Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
Melanie Bahlo1] Bioinformatics Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia. [2] Department of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia.
George M MartinDepartment of Pathology, University of Washington, Seattle, Washington, USA.
Cora M AalfsDepartment of Clinical Genetics, Amsterdam Medical Centre, Amsterdam, the Netherlands.
Junko OshimaDepartment of Pathology, University of Washington, Seattle, Washington, USA.
Janos TerzicDepartment of Immunology and Medical Genetics, University of Split, School of Medicine, Split, Croatia.
David J Amor1] Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia. [2] Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
Ivan Dikic1] Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt (Main), Germany. [2] Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt (Main), Germany.
Kristijan Ramadan1] Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK. [2] Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Zürich, Switzerland.
Christian Kubisch1] Institute of Human Genetics, University of Ulm, Ulm, Germany. [2] Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
University of Cologne · DEUniversität Ulm · DECancer Research UK · GBUniversity of Split · HRVictorian Clinical Genetics Services · AUWalter and Eliza Hall Institute of Medical Research · AUGoethe University Frankfurt · DEHospital Universitario de Canarias · ESMurdoch Children's Research Institute · AUUniversität Hamburg · DEUniversity of Washington · USUniversity of Zurich · CHLeibniz Institute on Aging - Fritz Lipmann Institute (FLI) · DERoyal Children's Hospital · AUThe University of Melbourne · AU
Funding
INTERNATIONAL REGISTRY OF WERNER SYNDROME/CELL BANKR24CA078088 · NCI · UNIVERSITY OF WASHINGTON · PI MARTIN, GEORGE M. · 1997 to 2011
$2.1MInternational Registry of Werner SyndromeR24AG042328 · NIA · UNIVERSITY OF WASHINGTON · PI MARTIN, GEORGE M., OSHIMA, JUNKO · 2012 to 2015
$743kNonsense-mediated decay array analysis of atypical Werner syndromeR21AG033313 · NIA · UNIVERSITY OF WASHINGTON · PI OSHIMA, JUNKO · 2009 to 2010
$352kEuropean Research Council 250241Medical Research Council MC_PC_12001/1NCI NIH HHS R24 CA078088NCI NIH HHS R24CA78088NIA NIH HHS R21 AG033313NIA NIH HHS R21AG033313NIA NIH HHS R24AG04232NIA NIH HHS R24 AG042328
Abstract
Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma.
Indexed as
Age of OnsetAnimalsBase SequenceCarcinoma, HepatocellularChromosome MappingCloning, MolecularDNA-Binding ProteinsDNA PrimersDNA ReplicationFlow CytometryFluorescent Antibody TechniqueGenes, cdcGenomic InstabilityGerm-Line MutationHumansLiver NeoplasmsDNA-Binding ProteinsDNA PrimersSPRTN protein, human
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