Evidence map›Paper›PMID 32853547›Full record

ArticleMolecular cell2020

DNA Structure-Specific Cleavage of DNA-Protein Crosslinks by the SPRTN Protease.

Hannah K Reinking, Hyun-Seo Kang, Maximilian J Götz, Hao-Yi Li, Anja Kieser, Shubo Zhao, Aleida C Acampora, Pedro Weickert, Evelyn Fessler, Lucas T Jae and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 59 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Hannah K ReinkingDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Hyun-Seo KangCenter for Integrated Protein Science Munich at the Department of Chemistry, Technical University of Munich, 85747 Garching, Germany; Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Maximilian J GötzDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Hao-Yi LiDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Anja KieserDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Shubo ZhaoDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Aleida C AcamporaDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Pedro WeickertDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Evelyn FesslerDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Lucas T JaeDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany.
Michael SattlerCenter for Integrated Protein Science Munich at the Department of Chemistry, Technical University of Munich, 85747 Garching, Germany; Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Julian StingeleDepartment of Biochemistry, Ludwig Maximilians University, 81377 Munich, Germany; Gene Center, Ludwig Maximilians University, 81377 Munich, Germany. Electronic address: stingele@genzentrum.lmu.de.
Ludwig-Maximilians-Universität München · DECenter for Integrated Protein Science Munich · DE

Funding

European Research Council 801750
6 · The paper itself

Abstract

Repair of covalent DNA-protein crosslinks (DPCs) by DNA-dependent proteases has emerged as an essential genome maintenance mechanism required for cellular viability and tumor suppression. However, how proteolysis is restricted to the crosslinked protein while leaving surrounding chromatin proteins unharmed has remained unknown. Using defined DPC model substrates, we show that the DPC protease SPRTN displays strict DNA structure-specific activity. Strikingly, SPRTN cleaves DPCs at or in direct proximity to disruptions within double-stranded DNA. In contrast, proteins crosslinked to intact double- or single-stranded DNA are not cleaved by SPRTN. NMR spectroscopy data suggest that specificity is not merely affinity-driven but achieved through a flexible bipartite strategy based on two DNA binding interfaces recognizing distinct structural features. This couples DNA context to activation of the enzyme, tightly confining SPRTN's action to biologically relevant scenarios.

Indexed as

Cell LineCross-Linking ReagentsDNADNA-Binding ProteinsHumansMagnetic Resonance SpectroscopyModels, BiologicalProtein DomainsStructure-Activity RelationshipCross-Linking ReagentsDNADNA-Binding ProteinsSPRTN protein, humanDNA-protein crosslinkDNA repairDNA structureformaldehydeproteaseSpartanSPRTNtopoisomerasesWss1

Identifiers

PMID32853547
PMCPMC7534798
OpenAlexW3080105230

What OpenQuestion holds

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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.