Evidence map›Paper›PMID 36350633›Full record

ArticleNucleic acids research2022

PARP1 proximity proteomics reveals interaction partners at stressed replication forks.

Thorsten Mosler, H Irem Baymaz, Justus F Gräf, Ivan Mikicic, Georges Blattner, Edward Bartlett, Matthias Ostermaier, Rossana Piccinno, Jiwen Yang, Andrea Voigt and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.9field-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

30 citing papers in PubMed, 47 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

17 authors at 4 institutions in 3 countries.

Thorsten MoslerInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
H Irem BaymazInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Justus F GräfInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Ivan MikicicInstitute of Molecular Biology (IMB), Mainz 55128, Germany.ORCID 0000-0003-3393-0688
Georges BlattnerInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Edward BartlettSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Matthias OstermaierInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Rossana PiccinnoInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Jiwen YangInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Andrea VoigtInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Marco GattiDepartment of Molecular Mechanisms of Disease, University of Zurich, Zurich CH-8057, Switzerland.
Stefania PellegrinoDepartment of Molecular Mechanisms of Disease, University of Zurich, Zurich CH-8057, Switzerland.
Matthias AltmeyerDepartment of Molecular Mechanisms of Disease, University of Zurich, Zurich CH-8057, Switzerland.
Katja LuckInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Ivan AhelSir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.ORCID 0000-0002-9446-3756
Vassilis RoukosInstitute of Molecular Biology (IMB), Mainz 55128, Germany.
Petra BeliInstitute of Molecular Biology (IMB), Mainz 55128, Germany.ORCID 0000-0001-9507-9820
Institute of Molecular Biology · DEUniversity of Zurich · CHUniversity of Oxford · GBJohannes Gutenberg University Mainz · DE

Funding

Cancer Research UK 22284Wellcome Trust 101794Wellcome Trust 210634Wellcome Trust 210634/Z/18/Z
6 · The paper itself

Abstract

PARP1 mediates poly-ADP-ribosylation of proteins on chromatin in response to different types of DNA lesions. PARP inhibitors are used for the treatment of BRCA1/2-deficient breast, ovarian, and prostate cancer. Loss of DNA replication fork protection is proposed as one mechanism that contributes to the vulnerability of BRCA1/2-deficient cells to PARP inhibitors. However, the mechanisms that regulate PARP1 activity at stressed replication forks remain poorly understood. Here, we performed proximity proteomics of PARP1 and isolation of proteins on stressed replication forks to map putative PARP1 regulators. We identified TPX2 as a direct PARP1-binding protein that regulates the auto-ADP-ribosylation activity of PARP1. TPX2 interacts with DNA damage response proteins and promotes homology-directed repair of DNA double-strand breaks. Moreover, TPX2 mRNA levels are increased in BRCA1/2-mutated breast and prostate cancers, and high TPX2 expression levels correlate with the sensitivity of cancer cells to PARP-trapping inhibitors. We propose that TPX2 confers a mitosis-independent function in the cellular response to replication stress by interacting with PARP1.

Indexed as

DNA ReplicationPoly (ADP-Ribose) Polymerase-1ProteomicsDNA Breaks, Double-StrandedDNA RepairPoly(ADP-ribose) Polymerase InhibitorsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID36350633
PMCPMC9723622
OpenAlexW4308616022

What OpenQuestion holds

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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.