Evidence map›Paper›PMID 21813623›Full record

ArticleGenome research2011

Genome-wide depletion of replication initiation events in highly transcribed regions.

Melvenia M Martin, Michael Ryan, RyangGuk Kim, Anna L Zakas, Haiqing Fu, Chii Mei Lin, William C Reinhold, Sean R Davis, Sven Bilke, Hongfang Liu and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing 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

96 citing papers in PubMed, 135 citations in OpenAlex.

  1. Review
  2. Why recombination hotspots?PLoS genetics · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Delineating highly transcribed noncoding elements landscape in breast cancer.Computational and structural biotechnology journal · 2023
    Article
  20. Safeguarding DNA Replication: A Golden Touch of MiDAS and Other Mechanisms.International journal of molecular sciences · 2022
    Review

36 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

16 authors at 5 institutions in 1 country.

Melvenia M MartinLaboratory of Molecular Pharmacology, CCR, NCI, Bethesda, Maryland 20892, USA.
Michael Ryan
RyangGuk Kim
Anna L Zakas
Haiqing Fu
Chii Mei Lin
William C Reinhold
Sean R Davis
Sven Bilke
Hongfang Liu
James H Doroshow
Mark A Reimers
Manuel S Valenzuela
Yves Pommier
Paul S Meltzer
Mirit I Aladjem
National Institutes of Health · USInsilicos (United States) · USMayo Clinic · USMeharry Medical College · USVirginia Commonwealth University · US

Funding

Initiation of DNA Replication in Mammalian CellsZIABC010411 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ALADJEM, MIRIT · 2009 to 2025
$25.0M
DNA Repair, Cell Cycle Checkpoints and Apoptosis as Targets for Anticancer DrugsZIABC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2009 to 2025
$23.0M
Cancer Genomics Technology DevelopmentZIABC011091 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MELTZER, PAUL S. · 2009 to 2025
$16.9M
Phase 01 Clinical TrialsZIABC011078 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DOROSHOW, JAMES · 2009 to 2025
$9.0M
Initiation Patterns of DNA Replication in Cancer Cell LinesSC1CA138180 · NCI · MEHARRY MEDICAL COLLEGE · PI VALENZUELA, MANUEL SEVERO · 2008 to 2011
$1.5M
Onto-BioThesaurus: ontological representation of gene/protein names for biomedicaR01LM009959 · NLM · MAYO CLINIC ROCHESTER · PI LIU, HONGFANG · 2009 to 2010
$1.2M
Howard Hughes Medical InstituteIntramural NIH HHSNCI NIH HHS CA138180NCI NIH HHS SC1 CA138180NLM NIH HHS R01 LM009959
6 · The paper itself

Abstract

This report investigates the mechanisms by which mammalian cells coordinate DNA replication with transcription and chromatin assembly. In yeast, DNA replication initiates within nucleosome-free regions, but studies in mammalian cells have not revealed a similar relationship. Here, we have used genome-wide massively parallel sequencing to map replication initiation events, thereby creating a database of all replication initiation sites within nonrepetitive DNA in two human cell lines. Mining this database revealed that genomic regions transcribed at moderate levels were generally associated with high replication initiation frequency. In genomic regions with high rates of transcription, very few replication initiation events were detected. High-resolution mapping of replication initiation sites showed that replication initiation events were absent from transcription start sites but were highly enriched in adjacent, downstream sequences. Methylation of CpG sequences strongly affected the location of replication initiation events, whereas histone modifications had minimal effects. These observations suggest that high levels of transcription interfere with formation of pre-replication protein complexes. Data presented here identify replication initiation sites throughout the genome, providing a foundation for further analyses of DNA-replication dynamics and cell-cycle progression.

Indexed as

DNA ReplicationGenome, HumanReplication OriginTranscription, GeneticCell Line, TumorChromatinCpG IslandsDNA MethylationGene Expression ProfilingGene Expression RegulationHumansK562 CellsTranscription Initiation SiteChromatin

Identifiers

PMID21813623
PMCPMC3205567
OpenAlexW2099929096

What OpenQuestion holds

Textmetadata
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.