Evidence map›Paper›PMID 31160578›Full record

ArticleNature communications2019

The ORC ubiquitin ligase OBI1 promotes DNA replication origin firing.

Philippe Coulombe, Joelle Nassar, Isabelle Peiffer, Slavica Stanojcic, Yvon Sterkers, Axel Delamarre, Stéphane Bocquet, Marcel Méchali

Abstract read
In one paragraph

Article in Nature communications, 2019. 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  3. Article
  4. The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024
    Review
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  11. HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma.International journal of molecular sciences · 2022
    Article
  12. Review
  13. Article
  14. Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1.International journal of molecular sciences · 2021
    Review
  15. Review
  16. Article
  17. Article
  18. RNF219/Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Article
  19. Article
  20. Article
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

8 authors.

Philippe CoulombeInstitute of Human Genetics, UMR 9002, CNRS-Université de Montpellier, 141 rue de la Cardonille, 34396, Montpellier, France. philippe.coulombe@igh.cnrs.fr.
Joelle NassarInstitute of Human Genetics, UMR 9002, CNRS-Université de Montpellier, 141 rue de la Cardonille, 34396, Montpellier, France.ORCID http://orcid.org/0000-0001-8267-5412
Isabelle PeifferInstitute of Human Genetics, UMR 9002, CNRS-Université de Montpellier, 141 rue de la Cardonille, 34396, Montpellier, France.
Slavica StanojcicCNRS 5290 - IRD 224 - University of Montpellier (UMR "MiVEGEC"), 34090, Montpellier, France.
Yvon SterkersCNRS 5290 - IRD 224 - University of Montpellier (UMR "MiVEGEC"), 34090, Montpellier, France.
Axel DelamarreInstitute of Human Genetics, UMR 9002, CNRS-Université de Montpellier, 141 rue de la Cardonille, 34396, Montpellier, France.
Stéphane BocquetInstitute of Human Genetics, UMR 9002, CNRS-Université de Montpellier, 141 rue de la Cardonille, 34396, Montpellier, France.
Marcel MéchaliInstitute of Human Genetics, UMR 9002, CNRS-Université de Montpellier, 141 rue de la Cardonille, 34396, Montpellier, France. marcel.mechali@igh.cnrs.fr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA replication initiation is a two-step process. During the G1-phase of the cell cycle, the ORC complex, CDC6, CDT1, and MCM2-7 assemble at replication origins, forming pre-replicative complexes (pre-RCs). In S-phase, kinase activities allow fork establishment through (CDC45/MCM2-7/GINS) CMG-complex formation. However, only a subset of all potential origins becomes activated, through a poorly understood selection mechanism. Here we analyse the pre-RC proteomic interactome in human cells and find C13ORF7/RNF219 (hereafter called OBI1, for ORC-ubiquitin-ligase-1) associated with the ORC complex. OBI1 silencing result in defective origin firing, as shown by reduced CMG formation, without affecting pre-RC establishment. OBI1 catalyses the multi-mono-ubiquitylation of a subset of chromatin-bound ORC3 and ORC5 during S-phase. Importantly, expression of non-ubiquitylable ORC3/5 mutants impairs origin firing, demonstrating their relevance as OBI1 substrates for origin firing. Our results identify a ubiquitin signalling pathway involved in origin activation and provide a candidate protein for selecting the origins to be fired.

Indexed as

DNA ReplicationG1 PhaseHumansOrigin Recognition ComplexProteomicsReplication OriginS PhaseUbiquitinationUbiquitin-Protein LigasesOBI1 protein, humanORC3 protein, humanORC5 protein, humanOrigin Recognition ComplexUbiquitin-Protein Ligases

Identifiers

PMID31160578
PMCPMC6547688

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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.