Evidence map›Paper›PMID 24668809›Full record

ArticleThe Journal of biological chemistry2014

The S229L colon tumor-associated variant of DNA polymerase β induces cellular transformation as a result of decreased polymerization efficiency.

Antonia A Nemec, Drew L Murphy, Katherine A Donigan, Joann B Sweasy

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair.International journal of molecular sciences · 2022
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Base Excision Repair Variants in Cancer.Methods in enzymology · 2017
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. 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

4 authors at 1 institution in 1 country.

Antonia A NemecFrom the Departments of Therapeutic Radiology and Genetics, Yale University, New Haven, Connecticut 06520.
Drew L MurphyFrom the Departments of Therapeutic Radiology and Genetics, Yale University, New Haven, Connecticut 06520.
Katherine A DoniganFrom the Departments of Therapeutic Radiology and Genetics, Yale University, New Haven, Connecticut 06520.
Joann B SweasyFrom the Departments of Therapeutic Radiology and Genetics, Yale University, New Haven, Connecticut 06520 joann.sweasy@yale.edu.
Yale University · US

Funding

DNA Polymerase Beta Variants and CancerR01ES019179 · NIEHS · YALE UNIVERSITY · PI SWEASY, JOANN B. · 2010 to 2020
$3.9M
RESEARCH TRAINING: RADIATION THERAPY, BIOLOGY, PHYSICST32CA009259 · NCI · YALE UNIVERSITY · PI GLAZER, PETER M · 1985 to 2009
$1.4M
Targeting Multiple DNA Repair Pathways to Increase Drug SensitivityF32CA156843 · NCI · YALE UNIVERSITY · PI NEMEC, ANTONIA A · 2011 to 2011
$51k
NCI NIH HHS F32 CA156843NCI NIH HHS T32 CA009259NIEHS NIH HHS ES019179NIEHS NIH HHS R01 ES019179
6 · The paper itself

Abstract

DNA polymerase β (Pol β) plays a key role in base excision repair (BER) by filling in small gaps that are generated after base adducts are excised from the DNA. Pol β is mutated in a large number of colorectal tumors, and these mutations may drive carcinogenesis. In the present study, we wished to determine whether the S229L somatic Pol β variant identified in a stage 3 colorectal tumor is a driver of carcinogenesis. We show that S229L does not possess any defects in binding to either DNA or nucleotides compared with the WT enzyme, but exhibits a significant loss of polymerization efficiency, largely due to an 8-fold decrease in the polymerization rate. S229L participates in BER, but due to its lower catalytic rate, does so more slowly than WT. Expression of S229L in mammalian cells induces the accumulation of BER intermediate substrates, chromosomal aberrations, and cellular transformation. Our results are consistent with the interpretation that S229L is a driver of carcinogenesis, likely as a consequence of its slow polymerization activity during BER in vivo.

Indexed as

MutationAnimalsBase SequenceCarcinogenesisCell LineCell Transformation, NeoplasticChromosome AberrationsColonic NeoplasmsDNADNA Polymerase betaDNA RepairGene Expression Regulation, EnzymologicGenomic InstabilityHumansKineticsMiceDNADNA Polymerase betaNucleotidesBase Excision RepairCancerGeneticsGenomic InstabilityMutagenesis

Identifiers

PMID24668809
PMCPMC4022845
OpenAlexW1970774923

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.