Evidence map›Paper›PMID 33683199›Full record

ArticleeLife2021

Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones.

Nina Kirstein, Alexander Buschle, Xia Wu, Stefan Krebs, Helmut Blum, Elisabeth Kremmer, Ina M Vorberg, Wolfgang Hammerschmidt, Laurent Lacroix, Olivier Hyrien and 2 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Cell cycle control of cohesion establishment.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Article
  15. DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Article
  16. Article
  17. Review
  18. Genes · 2022
    Review
  19. Review
  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

12 authors at 5 institutions in 2 countries.

Nina KirsteinResearch Unit Gene Vectors, Helmholtz Zentrum München (GmbH), German Research Center for Environmental Health, Munich, Germany.ORCID 0000-0001-6030-6173
Alexander BuschleResearch Unit Gene Vectors, Helmholtz Zentrum München (GmbH), German Research Center for Environmental Health and German Center for Infection Research (DZIF), Munich, Germany.
Xia WuInstitut de Biologie de l'ENS (IBENS), Département de Biologie, Ecole Normale Supérieure, CNRS, Inserm, PSL Research University, Paris, France.
Stefan KrebsLaboratory for Functional Genome Analysis (LAFUGA), Gene Center of the Ludwig-Maximilians Universität (LMU) München, Munich, Germany.
Helmut BlumLaboratory for Functional Genome Analysis (LAFUGA), Gene Center of the Ludwig-Maximilians Universität (LMU) München, Munich, Germany.
Elisabeth KremmerInstitute for Molecular Immunology, Monoclonal Antibody Core Facility, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Ina M VorbergGerman Center for Neurodegenerative Diseases (DZNE e.V.), Bonn, Germany.ORCID 0000-0003-0583-4015
Wolfgang HammerschmidtResearch Unit Gene Vectors, Helmholtz Zentrum München (GmbH), German Research Center for Environmental Health and German Center for Infection Research (DZIF), Munich, Germany.ORCID 0000-0002-4659-0427
Laurent LacroixInstitut de Biologie de l'ENS (IBENS), Département de Biologie, Ecole Normale Supérieure, CNRS, Inserm, PSL Research University, Paris, France.
Olivier HyrienInstitut de Biologie de l'ENS (IBENS), Département de Biologie, Ecole Normale Supérieure, CNRS, Inserm, PSL Research University, Paris, France.ORCID 0000-0001-8879-675X
Benjamin AuditUniv Lyon, ENS de Lyon, Univ. Claude Bernard, CNRS, Laboratoire de Physique, 69342 Lyon, France.ORCID 0000-0003-2683-9990
Aloys SchepersResearch Unit Gene Vectors, Helmholtz Zentrum München (GmbH), German Research Center for Environmental Health, Munich, Germany.ORCID 0000-0002-5442-5608
Helmholtz Zentrum München · DECentre National de la Recherche Scientifique · FRLudwig-Maximilians-Universität München · DEUniversité Claude Bernard Lyon 1 · FRUniversity of Bonn · DE

Funding

Genetic Analysis of EBV's Immortalizing GenesR01CA070723 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SUGDEN, WILLIAM M. · 1996 to 2017
$4.6M
NCI NIH HHS R01 CA070723
6 · The paper itself

Abstract

Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing, and fork directionality profiles obtained by RNA-seq, Repli-seq, and OK-seq. Both, the origin recognition complex (ORC) and the minichromosome maintenance complex (MCM) are significantly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early- than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating regions, and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late-replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms specifying when and where replication initiates in human cells.

Indexed as

Models, GeneticCell Line, TumorDNA ReplicationHumansMinichromosome Maintenance ProteinsOrigin Recognition ComplexMinichromosome Maintenance ProteinsOrigin Recognition ComplexchromosomesDNA replication initiationgene expressionH4K20 methylationhumanmouseok-seq, chip-seqorc, mcm complexreplication timingtranscription

Identifiers

PMID33683199
PMCPMC7993996
OpenAlexW3134744679

What OpenQuestion holds

Textmetadata
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.