Evidence map›Paper›PMID 26728715›Full record

ArticleGenome research2016

Quantitative BrdU immunoprecipitation method demonstrates that Fkh1 and Fkh2 are rate-limiting activators of replication origins that reprogram replication timing in G1 phase.

Jared M Peace, Sandra K Villwock, John L Zeytounian, Yan Gan, Oscar M Aparicio

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
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  7. Review
  8. Rpd3 regulates single-copy origins independently of the rDNA array by opposing Fkh1-mediated origin stimulation.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Article
  10. Article
  11. Unveiling Forkhead-mediated regulation of yeast cell cycle and metabolic networks.Computational and structural biotechnology journal · 2022
    Article
  12. Review
  13. Article
  14. Review
  15. Genomic methods for measuring DNA replication dynamics.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2020
    Review
  16. Article
  17. Review
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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

5 authors at 1 institution in 1 country.

Jared M PeaceMolecular and Computational Biology Program, University of Southern California, Los Angeles, California 90089-2910, USA.
Sandra K VillwockMolecular and Computational Biology Program, University of Southern California, Los Angeles, California 90089-2910, USA.
John L ZeytounianMolecular and Computational Biology Program, University of Southern California, Los Angeles, California 90089-2910, USA.
Yan GanMolecular and Computational Biology Program, University of Southern California, Los Angeles, California 90089-2910, USA.
Oscar M AparicioMolecular and Computational Biology Program, University of Southern California, Los Angeles, California 90089-2910, USA.
University of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Implications of haplotype structure in the human genomeP50HG002790 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TAVARE, SIMON · 2003 to 2013
$29.9M
Regulation of Chromosomal DNA Replication Dynamics in S. CerevisiaeR01GM065494 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI APARICIO, OSCAR M · 2003 to 2022
$6.9M
NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089NHGRI NIH HHS P50 HG002790NHGRI NIH HHS P50-HG002790NIGMS NIH HHS 2R01-GM065494NIGMS NIH HHS R01 GM065494
6 · The paper itself

Abstract

The Saccharomyces cerevisiae Forkhead Box (FOX) proteins, Fkh1 and Fkh2, regulate diverse cellular processes including transcription, long-range DNA interactions during homologous recombination, and replication origin timing and long-range origin clustering. We hypothesized that, as stimulators of early origin activation, Fkh1 and Fkh2 abundance limits the rate of origin activation genome-wide. Existing methods, however, are not well-suited to quantitative, genome-wide measurements of origin firing between strains and conditions. To overcome this limitation, we developed qBrdU-seq, a quantitative method for BrdU incorporation analysis of replication dynamics, and applied it to show that overexpression of Fkh1 and Fkh2 advances the initiation timing of many origins throughout the genome resulting in a higher total level of origin initiations in early S phase. The higher initiation rate is accompanied by slower replication fork progression, thereby maintaining a normal length of S phase without causing detectable Rad53 checkpoint kinase activation. The advancement of origin firing time, including that of origins in heterochromatic domains, was established in late G1 phase, indicating that origin timing can be reset subsequently to origin licensing. These results provide novel insights into the mechanisms of origin timing regulation by identifying Fkh1 and Fkh2 as rate-limiting factors for origin firing that determine the ability of replication origins to accrue limiting factors and have the potential to reprogram replication timing late in G1 phase.

Indexed as

DNA ReplicationDNA Replication TimingG1 PhaseReplication OriginBromodeoxyuridineCell Cycle ProteinsChromatin ImmunoprecipitationForkhead Transcription FactorsHigh-Throughput Nucleotide SequencingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsBromodeoxyuridineCell Cycle ProteinsFkh1 protein, S cerevisiaeFkh2 protein, S cerevisiaeForkhead Transcription FactorsSaccharomyces cerevisiae Proteins

Identifiers

PMID26728715
PMCPMC4772018
OpenAlexW2255778033

What OpenQuestion holds

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LicenceCC BY-NC
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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.