Evidence map›Paper›PMID 33348378›Full record

ArticleNucleic acids research2021

A ubiquitin switch controls autocatalytic inactivation of the DNA-protein crosslink repair protease SPRTN.

Shubo Zhao, Anja Kieser, Hao-Yi Li, Hannah K Reinking, Pedro Weickert, Simon Euteneuer, Denitsa Yaneva, Aleida C Acampora, Maximilian J Götz, Regina Feederle and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 44 citations in OpenAlex.

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  20. Targeting DNA-Protein CrosslinksFrontiers in molecular biosciences · 2022
    Review
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

11 authors at 2 institutions in 1 country.

Shubo ZhaoDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Anja KieserDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Hao-Yi LiDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Hannah K ReinkingDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Pedro WeickertDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Simon EuteneuerDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Denitsa YanevaDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Aleida C AcamporaDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Maximilian J GötzDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Regina FeederleInstitute for Diabetes and Obesity, Monoclonal Antibody Core Facility, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Julian StingeleDepartment of Biochemistry, Ludwig-Maximilians-University, 81377 Munich, Germany.
Ludwig-Maximilians-Universität München · DEHelmholtz Zentrum München · DE

Funding

European Research Council 801750
6 · The paper itself

Abstract

Repair of covalent DNA-protein crosslinks (DPCs) by the metalloprotease SPRTN prevents genome instability, premature aging and carcinogenesis. SPRTN is specifically activated by DNA structures containing single- and double-stranded features, but degrades the protein components of DPCs promiscuously and independent of amino acid sequence. This lack of specificity is useful to target diverse protein adducts, however, it requires tight control in return, in order to prohibit uncontrolled proteolysis of chromatin proteins. Here, we discover the components and principles of a ubiquitin switch, which negatively regulates SPRTN. We demonstrate that monoubiquitylation is induced in an E3 ligase-independent manner and, in contrast to previous assumptions, does not control chromatin access of the enzyme. Data obtained in cells and in vitro reveal that monoubiquitylation induces inactivation of the enzyme by triggering autocatalytic cleavage in trans while also priming SPRTN for proteasomal degradation in cis. Finally, we show that the deubiquitylating enzyme USP7 antagonizes this negative control of SPRTN in the presence of DPCs.

Indexed as

Protein Processing, Post-TranslationalUbiquitinationCatalysisCell LineChromatinDeubiquitinating EnzymesDNA AdductsDNA-Binding ProteinsDNA RepairGene Knockout TechniquesHumansProteasome Endopeptidase ComplexProteolysisRecombinant Fusion ProteinsRNA InterferenceRNA, Small InterferingChromatinDeubiquitinating EnzymesDNA AdductsDNA-Binding ProteinsProteasome Endopeptidase ComplexRecombinant Fusion ProteinsRNA, Small InterferingSPRTN protein, humanUbiquitinUbiquitin-Specific Peptidase 7USP7 protein, human

Identifiers

PMID33348378
PMCPMC7826251
OpenAlexW3118073226

What OpenQuestion holds

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LicenceCC BY
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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.