Evidence map›Paper›PMID 18803403›Full record

ArticleBiochemistry2008

Repair of O6-G-alkyl-O6-G interstrand cross-links by human O6-alkylguanine-DNA alkyltransferase.

Qingming Fang, Anne M Noronha, Sebastian P Murphy, Christopher J Wilds, Julie L Tubbs, John A Tainer, Goutam Chowdhury, F Peter Guengerich, Anthony E Pegg

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2008. 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
1.5field-weighted citation impact, top 19% 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, 48 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Mechanisms of DNA damage, repair, and mutagenesis.Environmental and molecular mutagenesis · 2017
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. DNA repair by reversal of DNA damage.Cold Spring Harbor perspectives in biology · 2013
    Review
  11. Review
  12. Review
  13. Article
  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

9 authors at 1 institution in 2 countries.

Qingming FangDepartments of Cellular and Molecular Physiology and Pharmacology, The Pennsylvania State University College of Medicine, P.O. Box 850, Hershey, Pennsylvania 17033, USA.
Anne M Noronha
Sebastian P Murphy
Christopher J Wilds
Julie L Tubbs
John A Tainer
Goutam Chowdhury
F Peter Guengerich
Anthony E Pegg
Scripps Research Institute · US

Funding

Structural Biology Facility CoreP30ES000267 · NIEHS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 1985 to 2014
$20.3M
BIOACTIVATION OF HALOGENATED HYDROCARBONSR01ES010546 · NIEHS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 2001 to 2020
$8.1M
Structural Biochemistry of DNA DealkylationR01CA097209 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI TAINER, JOHN A. · 2002 to 2014
$4.4M
PERSISTENCE OF ALKYLATED DNA IN CARCINOGENESISR01CA018137 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI KANUGULA, SREENIVAS · 1985 to 2011
$2.8M
PERSISTENCE OF ALKYLATED DNA IN CARCINOGENESISR37CA018137 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI PEGG, ANTHONY E · 1989 to 2009
$972k
NCI NIH HHS CA-018137NCI NIH HHS CA-097209NCI NIH HHS R01 CA018137NCI NIH HHS R01 CA097209NCI NIH HHS R37 CA018137NIEHS NIH HHS P30 ES000267NIEHS NIH HHS R01 ES010546NIEHS NIH HHS R01 ES10546
6 · The paper itself

Abstract

O (6)-Alkylguanine-DNA alkyltransferase (AGT) plays an important role by protecting cells from alkylating agents. This reduces the frequency of carcinogenesis and mutagenesis initiated by such agents, but AGT also provides a major resistance mechanism to some chemotherapeutic drugs. To improve our understanding of the AGT-mediated repair reaction and our understanding of the spectrum of repairable damage, we have studied the ability of AGT to repair interstrand cross-link DNA damage where the two DNA strands are joined via the guanine- O (6) in each strand. An oligodeoxyribonucleotide containing a heptane cross-link was repaired with initial formation of an AGT-oligo complex and further reaction of a second AGT molecule yielding a hAGT dimer and free oligo. However, an oligodeoxyribonucleotide with a butane cross-link was a very poor substrate for AGT-mediated repair, and only the first reaction that forms an AGT-oligo complex could be detected. Models of the reaction of these substrates in the AGT active site show that the DNA duplex is forced apart locally to repair the first guanine. This reaction is greatly hindered with the butane cross-link, which is mostly buried in the active site pocket and limited in conformational flexibility. This limitation also prevents the adoption of a conformation for the second reaction to repair the AGT-oligo complex. These results are consistent with the postulated mechanism of AGT repair that involves DNA binding and flipping of the substrate nucleotide and indicate that hAGT can repair some types of interstrand cross-link damage.

Indexed as

DNA RepairBlotting, WesternChromatography, High Pressure LiquidDNA DamageDNA Modification MethylasesDNA Repair EnzymesElectrophoresis, Polyacrylamide GelHumansModels, MolecularTumor Suppressor ProteinsDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTumor Suppressor Proteins

Identifiers

PMID18803403
PMCPMC2632579
OpenAlexW2015772815

What OpenQuestion holds

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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.