Evidence map›Paper›PMID 17452367›Full record

ArticleNucleic acids research2007

Regulation of B family DNA polymerase fidelity by a conserved active site residue: characterization of M644W, M644L and M644F mutants of yeast DNA polymerase epsilon.

Zachary F Pursell, Isabelle Isoz, Else-Britt Lundström, Erik Johansson, Thomas A Kunkel

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2007. 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
2.0field-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

32 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
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  14. Review
  15. DNA polymerase delta in DNA replication and genome maintenance.Environmental and molecular mutagenesis · 2012
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. The lower bound to the evolution of mutation rates.Genome biology and evolution · 2011
    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

5 authors at 3 institutions in 2 countries.

Zachary F PursellLaboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
Isabelle Isoz
Else-Britt Lundström
Erik Johansson
Thomas A Kunkel
National Institute of Environmental Health Sciences · USNational Institutes of Health · USUmeå University · SE

Funding

Structure-Function Studies Of DNA Replication FidelityZIAES065070 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 2009 to 2025
$30.6M
Structure-Function Studies Of DNA Replication FidelityZ01ES065070 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 1991 to 2008
$4.3M
Intramural NIH HHS
6 · The paper itself

Abstract

To better understand the functions and fidelity of DNA polymerase epsilon (Pol epsilon), we report here on the fidelity of yeast Pol epsilon mutants with leucine, tryptophan or phenylalanine replacing Met644. The Met644 side chain interacts with an invariant tyrosine that contacts the sugar of the incoming dNTP. M644W and M644L Pol epsilon synthesize DNA with high fidelity, but M644F Pol epsilon has reduced fidelity resulting from strongly increased misinsertion rates. When Msh6-dependent repair of replication errors is defective, the mutation rate of a pol2-M644F strain is 16-fold higher than that of a strain with wild-type Pol epsilon. In conjunction with earlier studies of low-fidelity mutants with replacements for the homologous amino acid in yeast Pol alpha (L868M/F) and Pol delta (L612M), these data indicate that the active site location occupied by Met644 in Pol epsilon is a key determinant of replication fidelity by all three B family replicative polymerases. Interestingly, error specificity of M644F Pol epsilon is distinct from that of L868M/F Pol alpha or L612M Pol delta, implying that each polymerase has different active site geometry, and suggesting that these polymerase alleles may generate distinctive mutational signatures for probing functions in vivo.

Indexed as

Amino Acid SubstitutionBinding SitesDNADNA Polymerase IIExodeoxyribonucleasesLeucineMethionineMutationPhenotypePhenylalanineSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTryptophanDNADNA Polymerase IIExodeoxyribonucleasesLeucineMethioninePhenylalanineSaccharomyces cerevisiae ProteinsTryptophan

Identifiers

PMID17452367
PMCPMC1888828
OpenAlexW1995150530

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.