Evidence map›Paper›PMID 32152270›Full record

ArticleNature communications2020

TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts.

John Fielden, Katherine Wiseman, Ignacio Torrecilla, Shudong Li, Samuel Hume, Shih-Chieh Chiang, Annamaria Ruggiano, Abhay Narayan Singh, Raimundo Freire, Sylvana Hassanieh and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

69 citing papers in PubMed, 100 citations in OpenAlex.

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9 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

17 authors at 4 institutions in 2 countries.

John Fielden *Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Katherine Wiseman *Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Ignacio TorrecillaCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0003-4283-0283
Shudong LiCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Samuel HumeCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0003-4417-0370
Shih-Chieh ChiangThe University of Sheffield Neuroscience Institute and the Healthy Lifespan Institute, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, S10 2TN, Sheffield, UK.
Annamaria RuggianoCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Abhay Narayan SinghCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Raimundo FreireUnidad de Investigación, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38320, La Laguna, Tenerife, Spain.ORCID http://orcid.org/0000-0003-4473-8894
Sylvana HassaniehCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Enric DomingoCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0003-4390-8767
Iolanda VendrellCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Roman FischerTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9715-5951
Benedikt M KesslerTDI Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8160-2446
Timothy S MaughanCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Sherif F El-KhamisyThe University of Sheffield Neuroscience Institute and the Healthy Lifespan Institute, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, S10 2TN, Sheffield, UK.ORCID http://orcid.org/0000-0003-2721-7763
Kristijan RamadanCancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK. kristijan.ramadan@oncology.ox.ac.uk.ORCID http://orcid.org/0000-0001-5522-021X
Cancer Research UK · GBUniversity of Oxford · GBUniversity of Sheffield · GBUniversidad de La Laguna · ES

Funding

Cancer Research UKMedical Research Council MC_EX_MR/K022830/1Medical Research Council MC_UU_00001/1Medical Research Council MR/M016587/1Wellcome TrustWellcome Trust 103844
6 · The paper itself

Abstract

Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient DNA replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate-a covalent TOP1-DNA adduct known as a TOP1 cleavage complex (TOP1cc)-is stabilised. TOP1ccs are highly cytotoxic and a failure to resolve them underlies the pathology of neurological disorders but is also exploited in cancer therapy where TOP1ccs are the target of widely used frontline anti-cancer drugs. A critical enzyme for TOP1cc resolution is the tyrosyl-DNA phosphodiesterase (TDP1), which hydrolyses the bond that links a tyrosine in the active site of TOP1 to a 3' phosphate group on a single-stranded (ss)DNA break. However, TDP1 can only process small peptide fragments from ssDNA ends, raising the question of how the ~90 kDa TOP1 protein is processed upstream of TDP1. Here we find that TEX264 fulfils this role by forming a complex with the p97 ATPase and the SPRTN metalloprotease. We show that TEX264 recognises both unmodified and SUMO1-modifed TOP1 and initiates TOP1cc repair by recruiting p97 and SPRTN. TEX264 localises to the nuclear periphery, associates with DNA replication forks, and counteracts TOP1ccs during DNA replication. Altogether, our study elucidates the existence of a specialised repair complex required for upstream proteolysis of TOP1ccs and their subsequent resolution.

Indexed as

Adenosine TriphosphatasesAmino Acid SequenceCell LineDNA AdductsDNA-Binding ProteinsDNA RepairDNA ReplicationDNA Topoisomerases, Type IEpistasis, GeneticHumansMembrane ProteinsNuclear ProteinsPhosphoric Diester HydrolasesSUMO-1 ProteinSumoylationAdenosine TriphosphatasesDNA AdductsDNA-Binding ProteinsDNA Topoisomerases, Type IMembrane ProteinsNuclear Proteinsp97 ATPasePhosphoric Diester HydrolasesSPRTN protein, humanSUMO-1 ProteinTDP1 protein, humanTEX264 protein, human

Identifiers

PMID32152270
PMCPMC7062751
OpenAlexW3009887985

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.