Evidence map›Paper›PMID 18799612›Full record

ArticleMolecular biology of the cell2008

The Hsk1(Cdc7) replication kinase regulates origin efficiency.

Prasanta K Patel, Naveen Kommajosyula, Adam Rosebrock, Aaron Bensimon, Janet Leatherwood, John Bechhoefer, Nicholas Rhind

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

48 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Article
  4. 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
  5. Article
  6. Genes · 2022
    Review
  7. NAR genomics and bioinformatics · 2021
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. DNA replication origin activation in space and time.Nature reviews. Molecular cell biology · 2015
    Review
  18. Article
  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

7 authors at 4 institutions in 3 countries.

Prasanta K PatelDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Naveen Kommajosyula
Adam Rosebrock
Aaron Bensimon
Janet Leatherwood
John Bechhoefer
Nicholas Rhind
University of Massachusetts Chan Medical School · USState University of New York · USInstitut Pasteur · FRSimon Fraser University · CA

Funding

The Role of MRN in the S-Phase DNA Damage CheckpointR01GM069957 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RHIND, NICHOLAS R · 2004 to 2013
$2.8M
Transcription circuitry of the S. pombe cell cycleR01GM076272 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI LEATHERWOOD, JANET K · 2007 to 2010
$1.1M
NCRR NIH HHS P40RR01632004NIGMS NIH HHS GM-069957NIGMS NIH HHS GM-076272NIGMS NIH HHS R01 GM069957NIGMS NIH HHS R01 GM076272
6 · The paper itself

Abstract

Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or decreasing Hsk1-Dfp1 levels correspondingly increases or decreases origin efficiency. Furthermore, tethering Hsk1-Dfp1 near an origin increases the efficiency of that origin, suggesting that the effective local concentration of Hsk1-Dfp1 regulates origin firing. Using photobleaching, we show that Hsk1-Dfp1 is freely diffusible in the nucleus. These results support a model in which the accessibility of replication origins to Hsk1-Dfp1 regulates origin efficiency and provides a potential mechanistic link between chromatin structure and replication timing. By manipulating Hsk1-Dfp1 levels, we show that increasing or decreasing origin firing rates leads to an increase in genomic instability, demonstrating the biological importance of appropriate origin efficiency.

Indexed as

DNA ReplicationReplication OriginCell Cycle ProteinsCell NucleusChromosomal InstabilityFluorescence Recovery After PhotobleachingGene Expression Regulation, FungalPlasmidsProtein KinasesProtein Serine-Threonine KinasesSchizosaccharomycesSchizosaccharomyces pombe ProteinsCell Cycle ProteinsDfp1 protein, S pombeHSK1 protein, S pombeProtein KinasesProtein Serine-Threonine KinasesSchizosaccharomyces pombe Proteins

Identifiers

PMID18799612
PMCPMC2592646
OpenAlexW2141380922

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.