Evidence map›Paper›PMID 26046662›Full record

ArticleHuman mutation2015

Somatic Mutations in Catalytic Core of POLK Reported in Prostate Cancer Alter Translesion DNA Synthesis.

Santosh Yadav, Sudurkia Mukhopadhyay, Muralidharan Anbalagan, Nick Makridakis

Open access · greenAbstract read
In one paragraph

Article in Human mutation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Mammalian DNA Polymerase Kappa Activity and Specificity.Molecules (Basel, Switzerland) · 2019
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Observational
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

4 authors at 1 institution in 1 country.

Santosh YadavTulane Cancer Center, Tulane University, New Orleans, Louisiana.
Sudurkia MukhopadhyayTulane Cancer Center, Tulane University, New Orleans, Louisiana.
Muralidharan AnbalaganStructural and Cellular Biology, Tulane University, New Orleans, Louisiana.
Nick MakridakisTulane Cancer Center, Tulane University, New Orleans, Louisiana.
Tulane University · US

Funding

UNCOVERING THE MECHANISMS OF OSTEOSARCOMA METASTASIS SUPPRESSION BY MTBPP20RR020152 · NCRR · TULANE UNIVERSITY OF LOUISIANA · PI FORTGANG, ILANA · 2004 to 2011
$17.0M
Mentoring a Cancer Genetics ProgramP20GM103518 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI DEININGER, PRESCOTT L. · 2012 to 2013
$4.3M
NCRR NIH HHS P20 RR020152NIGMS NIH HHS P20 GM103518
6 · The paper itself

Abstract

DNA polymerase kappa is a Y-family polymerase that participates to bypass the damaged DNA known as translesion synthesis (TLS) polymerase. Higher frequency of mutations in DNA polymerase kappa (POLK) recently been reported in prostate cancer. We sequenced entire exons of the POLK gene on genomic DNA from 40 prostate cancers and matched normal samples. We identified that 28% of patients have somatic mutations in the POLK gene of the prostate tumors. Mutations in these prostate cancers have somatic mutation spectra, which are dominated by C-to-T transitions. In the current study, we further investigate the effect of p.E29K, p.G154E, p.F155S, p.E430K, p.L442F, and p.E449K mutations on the biochemical properties of the polymerase in vitro, using TLS assay and nucleotide incorporation fidelity, following site-directed mutagenesis bacterial expression, and purification of the respective polymerase variants. We report that following missense mutations p.E29K, p.G154E, p.F155S, p.E430K, and p.L442F significantly diminished the catalytic efficiencies of POLK with regard to the lesion bypass (AP site). POLK variants show extraordinarily low fidelity by misincorporating T, C, and G as compared to wild-type variants. Taken together, these results suggest that interfering with normal polymerase kappa function by these mutations may be involved in prostate carcinogenesis.

Indexed as

DNA ReplicationMutationAgedBase CompositionCase-Control StudiesCatalysisCatalytic DomainDNA-Directed DNA PolymeraseEnzyme ActivationExonsGene ExpressionHumansKineticsMaleMiddle AgedModels, MolecularDNA-Directed DNA PolymerasePOLK protein, humanY-Family DNA Polymerasescatalytic efficienciesmissense mutationspolymerase kappaprostate cancertranslesion synthesis

Identifiers

PMID26046662
PMCPMC4537374
OpenAlexW1593008412

What OpenQuestion holds

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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.