Evidence map›Paper›PMID 25868109›Full record

ArticlePLoS genetics2015

Volatility of Mutator Phenotypes at Single Cell Resolution.

Scott R Kennedy, Eric M Schultz, Thomas M Chappell, Brendan Kohrn, Gary M Knowels, Alan J Herr

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. How Should Cancer Models Be Constructed?Cancer control : journal of the Moffitt Cancer Center
    Review
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

6 authors at 2 institutions in 1 country.

Scott R KennedyDepartment of Pathology, University of Washington, Seattle, Washington, United States of America.
Eric M SchultzDepartment of Pathology, University of Washington, Seattle, Washington, United States of America.
Thomas M ChappellDepartment of Entomology, North Carolina State University, Raleigh, North Carolina, United States of America.
Brendan KohrnDepartment of Pathology, University of Washington, Seattle, Washington, United States of America.
Gary M KnowelsDepartment of Pathology, University of Washington, Seattle, Washington, United States of America.
Alan J HerrDepartment of Pathology, University of Washington, Seattle, Washington, United States of America.
University of Washington · USNorth Carolina State University · US

Funding

GENETIC APPROACHES TO AGING RESEARCHT32AG000057 · NIA · UNIVERSITY OF WASHINGTON · PI RABINOVITCH, PETER S · 1985 to 2019
$14.2M
Suppressors of Eukaryotic Mutator PhenotypesR21ES021544 · NIEHS · UNIVERSITY OF WASHINGTON · PI HERR, ALAN J · 2013 to 2014
$410k
NIA NIH HHS R03 AG03708NIA NIH HHS T32 AG000057NIA NIH HHS T32-AG000057NIEHS NIH HHS R21 ES021544
6 · The paper itself

Abstract

Mutator phenotypes accelerate the evolutionary process of neoplastic transformation. Historically, the measurement of mutation rates has relied on scoring the occurrence of rare mutations in target genes in large populations of cells. Averaging mutation rates over large cell populations assumes that new mutations arise at a constant rate during each cell division. If the mutation rate is not constant, an expanding mutator population may contain subclones with widely divergent rates of evolution. Here, we report mutation rate measurements of individual cell divisions of mutator yeast deficient in DNA polymerase ε proofreading and base-base mismatch repair. Our data are best fit by a model in which cells can assume one of two distinct mutator states, with mutation rates that differ by an order of magnitude. In error-prone cell divisions, mutations occurred on the same chromosome more frequently than expected by chance, often in DNA with similar predicted replication timing, consistent with a spatiotemporal dimension to the hypermutator state. Mapping of mutations onto predicted replicons revealed that mutations were enriched in the first half of the replicon as well as near termination zones. Taken together, our findings show that individual genome replication events exhibit an unexpected volatility that may deepen our understanding of the evolution of mutator-driven malignancies.

Indexed as

Mutation RateAllelesBase Pair MismatchCell DivisionDNA, FungalDNA Mismatch RepairDNA Polymerase IIDNA ReplicationGenome, FungalPhenotypeRepliconSequence Analysis, DNAYeastsDNA, FungalDNA Polymerase II

Identifiers

PMID25868109
PMCPMC4395103
OpenAlexW2065543717

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.