Evidence map›Paper›PMID 27871365›Full record

ArticleMolecular cell2016

Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN.

Julian Stingele, Roberto Bellelli, Ferdinand Alte, Graeme Hewitt, Grzegorz Sarek, Sarah L Maslen, Susan E Tsutakawa, Annabel Borg, Svend Kjær, John A Tainer and 3 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 150 papers.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed
11.5field-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

150 citing papers in PubMed, 244 citations in OpenAlex.

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  16. 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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90 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

13 authors at 5 institutions in 3 countries.

Julian StingeleThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Roberto BellelliThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Ferdinand AlteCenter for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
Graeme HewittThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Grzegorz SarekThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Sarah L MaslenMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Susan E TsutakawaMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Annabel BorgThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Svend KjærThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
John A TainerMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Mark SkehelMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Michael GrollCenter for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
Simon J BoultonThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: simon.boulton@crick.ac.uk.
The Francis Crick Institute · GBCenter for Integrated Protein Science Munich · DEMRC Laboratory of Molecular Biology · GBLawrence Berkeley National Laboratory · USThe University of Texas MD Anderson Cancer Center · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Cancer Research UK 11581Cancer Research UK FC0010048Medical Research Council FC0010048Medical Research Council MC_U105178788NCI NIH HHS P01 CA092584Wellcome Trust FC0010048
6 · The paper itself

Abstract

Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled by several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define a DNA switch triggering its protease activity, a ubiquitin switch controlling SPRTN chromatin accessibility, and regulatory autocatalytic cleavage. Our data also provide a molecular explanation on how SPRTN deficiency causes the premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.

Indexed as

DNA RepairAmino Acid SequenceAnimalsBinding SitesCaenorhabditis elegansCaenorhabditis elegans ProteinsCell LineCisplatinCross-Linking ReagentsCrystallography, X-RayDNADNA-Binding ProteinsFibroblastsFormaldehydeHeLa CellsHumansCaenorhabditis elegans ProteinsCisplatinCross-Linking ReagentsDNADNA-Binding ProteinsFormaldehydeSchizosaccharomyces pombe ProteinsSPRTN protein, humanXeroderma Pigmentosum Group A ProteinXPA-1 protein, C elegansDNA-protein crosslinksDNA repairDVC1formaldehydehepatocellular carcinomaprogeriaproteaseRuijs-Aalfs syndromeSpartanSPRTNtopoisomeraseWss1

Identifiers

PMID27871365
PMCPMC5128726
OpenAlexW2542256116

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.