Evidence map›Paper›PMID 36681662›Full record

ArticleNature communications2023

SPRTN patient variants cause global-genome DNA-protein crosslink repair defects.

Pedro Weickert, Hao-Yi Li, Maximilian J Götz, Sophie Dürauer, Denitsa Yaneva, Shubo Zhao, Jacqueline Cordes, Aleida C Acampora, Ignasi Forne, Axel Imhof and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

24 citing papers in PubMed, 32 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

11 authors at 2 institutions in 1 country.

Pedro Weickert *Department of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.
Hao-Yi Li *Department of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.
Maximilian J GötzDepartment of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.
Sophie DürauerDepartment of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.
Denitsa YanevaDepartment of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.
Shubo ZhaoDepartment of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.
Jacqueline CordesDepartment of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.ORCID http://orcid.org/0000-0001-9117-3916
Aleida C AcamporaDepartment of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.
Ignasi ForneProtein Analysis Unit (ZfP), BioMedical Center (BMC), Ludwig-Maximilians-University, 82152, Martinsried, Germany.ORCID http://orcid.org/0000-0003-0309-907X
Axel ImhofProtein Analysis Unit (ZfP), BioMedical Center (BMC), Ludwig-Maximilians-University, 82152, Martinsried, Germany.ORCID http://orcid.org/0000-0003-2993-8249
Julian StingeleDepartment of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany. stingele@genzentrum.lmu.de.ORCID http://orcid.org/0000-0001-6020-2075
Ludwig-Maximilians-Universität München · DECenter for Integrated Protein Science Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA-protein crosslinks (DPCs) are pervasive DNA lesions that are induced by reactive metabolites and various chemotherapeutic agents. Here, we develop a technique for the Purification of x-linked Proteins (PxP), which allows identification and tracking of diverse DPCs in mammalian cells. Using PxP, we investigate DPC repair in cells genetically-engineered to express variants of the SPRTN protease that cause premature ageing and early-onset liver cancer in Ruijs-Aalfs syndrome patients. We find an unexpected role for SPRTN in global-genome DPC repair, that does not rely on replication-coupled detection of the lesion. Mechanistically, we demonstrate that replication-independent DPC cleavage by SPRTN requires SUMO-targeted ubiquitylation of the protein adduct and occurs in addition to proteasomal DPC degradation. Defective ubiquitin binding of SPRTN patient variants compromises global-genome DPC repair and causes synthetic lethality in combination with a reduction in proteasomal DPC repair capacity.

Indexed as

DNA-Binding ProteinsDNA DamageAnimalsDNA RepairHumansMammalsProteasome Endopeptidase ComplexDNA-Binding ProteinsProteasome Endopeptidase ComplexSPRTN protein, human

Identifiers

PMID36681662
PMCPMC9867749
OpenAlexW4317659311

What OpenQuestion holds

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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.