Evidence map›Paper›PMID 24695738›Full record

ArticleThe Journal of biological chemistry2014

Base excision repair of tandem modifications in a methylated CpG dinucleotide.

Akira Sassa, Melike Çağlayan, Nadezhda S Dyrkheeva, William A Beard, Samuel H Wilson

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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-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

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  5. The genomics of oxidative DNA damage, repair, and resulting mutagenesis.Computational and structural biotechnology journal · 2020
    Review
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  7. Article
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  12. Review
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  14. Capturing snapshots of APE1 processing DNA damage.Nature structural & molecular biology · 2015
    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

5 authors at 2 institutions in 2 countries.

Akira SassaFrom the Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 and.
Melike ÇağlayanFrom the Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 and.
Nadezhda S DyrkheevaFrom the Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 and Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Science, 630090 Novosibirsk, Russia.
William A BeardFrom the Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 and.
Samuel H WilsonFrom the Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 and wilson5@niehs.nih.gov.
National Institute of Environmental Health Sciences · USNational Institutes of Health · US

Funding

Mechanisms of Nucleic Acid Enzymes - Pol Beta, HIV-1 Reverse Transcriptase and Mammalian Base Repair EnzymesZIAES050158 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 2009 to 2022
$17.0M
Molecular Mechanisms of Human DNA Polymerase Beta Catalysis, Fidelity and Selective InhibitionU19CA177547 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOODMAN, MYRON · 2013 to 2017
$5.5M
BIOLOGY OF MAMMALIAN BASE EXCISION REPAIRZ01ES050159 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$4.5M
Nucleic Acid Enzymes--Pol Beta And Base Repair EnzymesZ01ES050158 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$2.8M
Intramural NIH HHS Z01 ES050158Intramural NIH HHS Z01 ES050159NCI NIH HHS U19 CA177547
6 · The paper itself

Abstract

Cytosine methylation and demethylation in tracks of CpG dinucleotides is an epigenetic mechanism for control of gene expression. The initial step in the demethylation process can be deamination of 5-methylcytosine producing the TpG alteration and T:G mispair, and this step is followed by thymine DNA glycosylase (TDG) initiated base excision repair (BER). A further consideration is that guanine in the CpG dinucleotide may become oxidized to 7,8-dihydro-8-oxoguanine (8-oxoG), and this could affect the demethylation process involving TDG-initiated BER. However, little is known about the enzymology of BER of altered in-tandem CpG dinucleotides; e.g. Tp8-oxoG. Here, we investigated interactions between this altered dinucleotide and purified BER enzymes, the DNA glycosylases TDG and 8-oxoG DNA glycosylase 1 (OGG1), apurinic/apyrimidinic (AP) endonuclease 1, DNA polymerase β, and DNA ligases. The overall TDG-initiated BER of the Tp8-oxoG dinucleotide is significantly reduced. Specifically, TDG and DNA ligase activities are reduced by a 3'-flanking 8-oxoG. In contrast, the OGG1-initiated BER pathway is blocked due to the 5'-flanking T:G mispair; this reduces OGG1, AP endonuclease 1, and DNA polymerase β activities. Furthermore, in TDG-initiated BER, TDG remains bound to its product AP site blocking OGG1 access to the adjacent 8-oxoG. These results reveal BER enzyme specificities enabling suppression of OGG1-initiated BER and coordination of TDG-initiated BER at this tandem alteration in the CpG dinucleotide.

Indexed as

DNA MethylationDNA RepairBase PairingBase Pair MismatchBase SequenceBinding SitesCpG IslandsDNADNA-(Apurinic or Apyrimidinic Site) LyaseDNA GlycosylasesGuanineHumansThymine DNA Glycosylase7,8-dihydro-8-oxoguanineAPEX1 protein, humanDNADNA-(Apurinic or Apyrimidinic Site) LyaseDNA GlycosylasesGuanineoxoguanine glycosylase 1, humanThymine DNA Glycosylase8-OxoguanineBase Excision RepairDNA DamageDNA DemethylationDNA GlycosylaseDNA MethylationDNA PolymeraseOxidative Stress

Identifiers

PMID24695738
PMCPMC4022870
OpenAlexW2074120812

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.