Evidence map›Paper›PMID 25837992›Full record

ArticleNucleic acids research2015

Next-generation sequencing reveals the biological significance of the N(2),3-ethenoguanine lesion in vivo.

Shiou-chi Chang, Bogdan I Fedeles, Jie Wu, James C Delaney, Deyu Li, Linlin Zhao, Plamen P Christov, Emily Yau, Vipender Singh, Marco Jost and 6 more

Open access · goldAbstract 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 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Etheno adducts: from tRNA modifications to DNA adducts and back to miscoding ribonucleotides.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021
    Review
  6. Article
  7. Article
  8. Recognition of 1,The Journal of biological chemistry · 2020
    Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Chemical Analysis of DNA Damage.Analytical chemistry · 2018
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

16 authors at 2 institutions in 1 country.

Shiou-chi ChangDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Bogdan I FedelesDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Jie WuBioMicro Center, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
James C DelaneyDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Deyu LiDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Linlin ZhaoDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, United States Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37232, United States.
Plamen P ChristovDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, United States Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37232, United States Department of Chemistry, Vanderbilt University, Nashville, TN 37232, United States.
Emily YauDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Vipender SinghDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Marco JostDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Catherine L DrennanDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Lawrence J MarnettDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, United States Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37232, United States Department of Chemistry, Vanderbilt University, Nashville, TN 37232, United States Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, United States.
Carmelo J RizzoDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, United States Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37232, United States Department of Chemistry, Vanderbilt University, Nashville, TN 37232, United States Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, United States.
Stuart S LevineBioMicro Center, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
F Peter GuengerichDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, United States Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37232, United States Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, United States.
John M EssigmannDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, United States Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States jessig@mit.edu.
Massachusetts Institute of Technology · USVanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 1985 to 2020
$25.6M
Reaction and Diffusion of NO in Biological SystemsP01CA026731 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1985 to 2018
$25.4M
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
SYNTHETIC APPROACHES TO PAH-ADDUCTED NUCLEOTIDESP01ES005355 · NIEHS · VANDERBILT UNIVERSITY · PI STONE, MICHAEL P · 1991 to 2010
$13.4M
TRAINING GRANTS IN ENVIROMENTAL TOXICOLOGYT32ES007020 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1985 to 2024
$13.1M
BIOACTIVATION OF HALOGENATED HYDROCARBONSR01ES010546 · NIEHS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 2001 to 2020
$8.1M
Intra and Extra-Chromosomal Probes for Mutagenesis by CarcinogensR01CA080024 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1998 to 2025
$5.9M
Intra- and Extra-Chromosomal Probes for Mutagenesis by CarcinogensR37CA080024 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 2008 to 2015
$3.1M
Complex Metallocluster Structure and AssemblyR01GM069857 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DRENNAN, CATHERINE L · 2004 to 2017
$3.1M
ACQUISITION OF A 500 MHZ LC-NMR: PEPTIDE CHEMISTRYS10RR019022 · NCRR · VANDERBILT UNIVERSITY · PI RIZZO, CARMELO J · 2005 to 2005
$500k
Howard Hughes Medical InstituteNCI NIH HHS P01 CA026731NCI NIH HHS P01 CA160032NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA080024NCI NIH HHS R37 CA080024NCRR NIH HHS S10 RR019022NIEHS NIH HHS P01 ES005355NIEHS NIH HHS P01 ES05355NIEHS NIH HHS P30 ES000267NIEHS NIH HHS P30 ES002109NIEHS NIH HHS R01 ES010546NIEHS NIH HHS T32 ES007020NIGMS NIH HHS R01 GM069857
6 · The paper itself

Abstract

Etheno DNA adducts are a prevalent type of DNA damage caused by vinyl chloride (VC) exposure and oxidative stress. Etheno adducts are mutagenic and may contribute to the initiation of several pathologies; thus, elucidating the pathways by which they induce cellular transformation is critical. Although N(2),3-ethenoguanine (N(2),3-εG) is the most abundant etheno adduct, its biological consequences have not been well characterized in cells due to its labile glycosidic bond. Here, a stabilized 2'-fluoro-2'-deoxyribose analog of N(2),3-εG was used to quantify directly its genotoxicity and mutagenicity. A multiplex method involving next-generation sequencing enabled a large-scale in vivo analysis, in which both N(2),3-εG and its isomer 1,N(2)-ethenoguanine (1,N(2)-εG) were evaluated in various repair and replication backgrounds. We found that N(2),3-εG potently induces G to A transitions, the same mutation previously observed in VC-associated tumors. By contrast, 1,N(2)-εG induces various substitutions and frameshifts. We also found that N(2),3-εG is the only etheno lesion that cannot be repaired by AlkB, which partially explains its persistence. Both εG lesions are strong replication blocks and DinB, a translesion polymerase, facilitates the mutagenic bypass of both lesions. Collectively, our results indicate that N(2),3-εG is a biologically important lesion and may have a functional role in VC-induced or inflammation-driven carcinogenesis.

Indexed as

DNA DamageMutationDioxygenasesDNA AdductsDNA Polymerase betaDNA RepairDNA Repair EnzymesGuanineHigh-Throughput Nucleotide SequencingMutagenesisSequence Analysis, DNASequence DeletionDioxygenasesDNA AdductsDNA Polymerase betaDNA Repair EnzymesGuanineN(2),3-ethenoguanine

Identifiers

PMID25837992
PMCPMC4477646
OpenAlexW1975384402

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.