Evidence map›Paper›PMID 26220181›Full record

ArticleNucleic acids research2015

DNA polymerases κ and ζ cooperatively perform mutagenic translesion synthesis of the C8-2'-deoxyguanosine adduct of the dietary mutagen IQ in human cells.

Arindam Bose, Paritosh Pande, Vijay P Jasti, Amy D Millsap, Edward K Hawkins, Carmelo J Rizzo, Ashis K Basu

Abstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
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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.

Arindam BoseDepartment of Chemistry, University of Connecticut, Storrs, CT 06269, USA.
Paritosh PandeDepartment of Chemistry, University of Connecticut, Storrs, CT 06269, USA.
Vijay P JastiDepartment of Chemistry, University of Connecticut, Storrs, CT 06269, USA.
Amy D MillsapDepartment of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
Edward K HawkinsDepartment of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
Carmelo J RizzoDepartment of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
Ashis K BasuDepartment of Chemistry, University of Connecticut, Storrs, CT 06269, USA ashis.basu@uconn.edu.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Structural Biology Facility CoreP30ES000267 · NIEHS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 1985 to 2014
$20.3M
Synthetic Approaches to Carcinogen-Linked OligonucleotidesP01CA160032 · NCI · VANDERBILT UNIVERSITY · PI STONE, MICHAEL P · 2012 to 2022
$14.0M
Genotoxicity and Repair of Tobacco-Specific Nitrosamine DNA AdductsR01ES021762 · NIEHS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SPRATT, THOMAS E · 2012 to 2022
$3.7M
BIOLOGICAL EFFECTS OF DNA ADDUCTS FORMED BY NITROPYRENESR01ES009127 · NIEHS · UNIVERSITY OF CONNECTICUT STORRS · PI BASU, ASHIS K, SUO, ZUCAI · 1998 to 2014
$3.5M
Synthesis, StructUre and Replication of Carcirogen-Modified OligonucleotidesR01ES016561 · NIEHS · VANDERBILT UNIVERSITY · PI RIZZO, CARMELO J · 2010 to 2014
$1.7M
Biological Effects of DNA Adducts Formed by Nitroaromatic CompoundsR56ES009127 · NIEHS · UNIVERSITY OF CONNECTICUT STORRS · PI BASU, ASHIS K, SUO, ZUCAI · 2009 to 2009
$393k
NCI NIH HHS P01 CA160032NCI NIH HHS P30 CA068485NIEHS NIH HHS ES016561NIEHS NIH HHS ES021762NIEHS NIH HHS ES09127NIEHS NIH HHS P30 ES000267NIEHS NIH HHS P30ES000267NIEHS NIH HHS R01 ES009127NIEHS NIH HHS R01 ES016561NIEHS NIH HHS R01 ES021762
6 · The paper itself

Abstract

The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8-2'-deoxyguanosine adduct (dG-C8-IQ) formed by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a highly mutagenic and carcinogenic heterocyclic amine found in cooked meats, were investigated. Three plasmid vectors containing the dG-C8-IQ adduct at the G1-, G2- or G3-positions of the NarI site (5'-G1G2CG3CC-3') were replicated in HEK293T cells. Fifty percent of the progeny from the G3 construct were mutants, largely G→T, compared to 18% and 24% from the G1 and G2 constructs, respectively. Mutation frequency (MF) of dG-C8-IQ was reduced by 38-67% upon siRNA knockdown of pol κ, whereas it was increased by 10-24% in pol η knockdown cells. When pol κ and pol ζ were simultaneously knocked down, MF of the G1 and G3 constructs was reduced from 18% and 50%, respectively, to <3%, whereas it was reduced from 24% to <1% in the G2 construct. In vitro TLS using yeast pol ζ showed that it can extend G3*:A pair more efficiently than G3*:C pair, but it is inefficient at nucleotide incorporation opposite dG-C8-IQ. We conclude that pol κ and pol ζ cooperatively carry out the majority of the error-prone TLS of dG-C8-IQ, whereas pol η is involved primarily in its error-free bypass.

Indexed as

DNA AdductsMutagensQuinolinesDeoxyguanosineDNADNA-Directed DNA PolymeraseHEK293 CellsHumansMutation RateY-Family DNA Polymerases2-amino-3-methylimidazo(4,5-f)quinolineC8-2'-deoxyguanosine-2-amino-3-methylimadazo(4,5-f)-quinoline adductDeoxyguanosineDNADNA AdductsDNA-Directed DNA PolymeraseDNA polymerase zetaMutagensPOLK protein, humanQuinolinesRad30 proteinY-Family DNA Polymerases

Identifiers

PMID26220181
PMCPMC4787813

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