Evidence map›Paper›PMID 27806303›Full record

ArticleCell reports2016

Hydroxyurea-Mediated Cytotoxicity Without Inhibition of Ribonucleotide Reductase.

Li Phing Liew, Zun Yi Lim, Matan Cohen, Ziqing Kong, Lisette Marjavaara, Andrei Chabes, Stephen D Bell

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Revised mechanism of hydroxyurea-induced cell cycle arrest and an improved alternative.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Phenotypic Characterization ofFrontiers in microbiology · 2021
    Article
  12. Development of anMolecular therapy. Methods & clinical development · 2020
    Article
  13. Article
  14. Review
  15. Versatility of the Mec1Current genetics · 2019
    Review
  16. Initiating DNA replication: a matter of prime importance.Biochemical Society transactions · 2019
    Review
  17. Article
  18. Article
  19. An archaeal primase functions as a nanoscale caliper to define primer length.Proceedings of the National Academy of Sciences of the United States of America · 2018
    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

7 authors at 2 institutions in 2 countries.

Li Phing LiewSir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
Zun Yi LimDepartment of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB, 212 South Hawthorne Drive, Bloomington, IN 47405, USA.
Matan CohenDepartment of Biology, Indiana University, Simon Hall MSB, 212 South Hawthorne Drive, Bloomington, IN 47405, USA.
Ziqing KongDepartment of Medical Biochemistry and Biophysics, Umeå University, SE 90197 Umeå, Sweden.
Lisette MarjavaaraDepartment of Medical Biochemistry and Biophysics, Umeå University, SE 90197 Umeå, Sweden.
Andrei ChabesDepartment of Medical Biochemistry and Biophysics, Umeå University, SE 90197 Umeå, Sweden; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE 90197 Umeå, Sweden.
Stephen D BellDepartment of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB, 212 South Hawthorne Drive, Bloomington, IN 47405, USA; Department of Biology, Indiana University, Simon Hall MSB, 212 South Hawthorne Drive, Bloomington, IN 47405, USA. Electronic address: stedbell@indiana.edu.
Indiana University Bloomington · USUmeå University · SE

Funding

Graduate Program in Quantitative and Chemical Biology at Indiana University BloomT32GM109825 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI GIEDROC, DAVID P. · 2014 to 2018
$926k
Biotechnology and Biological Sciences Research CouncilNIGMS NIH HHS T32 GM109825Wellcome Trust
6 · The paper itself

Abstract

In many organisms, hydroxyurea (HU) inhibits class I ribonucleotide reductase, leading to lowered cellular pools of deoxyribonucleoside triphosphates. The reduced levels for DNA precursors is believed to cause replication fork stalling. Upon treatment of the hyperthermophilic archaeon Sulfolobus solfataricus with HU, we observe dose-dependent cell cycle arrest, accumulation of DNA double-strand breaks, stalled replication forks, and elevated levels of recombination structures. However, Sulfolobus has a HU-insensitive class II ribonucleotide reductase, and we reveal that HU treatment does not significantly impact cellular DNA precursor pools. Profiling of protein and transcript levels reveals modulation of a specific subset of replication initiation and cell division genes. Notably, the selective loss of the regulatory subunit of the primase correlates with cessation of replication initiation and stalling of replication forks. Furthermore, we find evidence for a detoxification response induced by HU treatment.

Indexed as

Bacterial ProteinsCell DivisionDNA, ArchaealDNA PrimaseDNA ReplicationGene Expression Regulation, ArchaealHydroxyureaNucleotidesProtein SubunitsRibonucleotide ReductasesRNA, MessengerSubstrate SpecificitySulfolobusTranscription, GeneticBacterial ProteinsDNA, ArchaealDNA PrimaseHydroxyureaNucleotidesProtein SubunitsRibonucleotide ReductasesRNA, MessengerarchaeaDNA damageDNA replicationhydroxyureareplication forkSulfolobus

Identifiers

PMID27806303
PMCPMC5134839
OpenAlexW2546869658

What OpenQuestion holds

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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.