Evidence map›Paper›PMID 25712093›Full record

ArticleNucleic acids research2015

Lesion search and recognition by thymine DNA glycosylase revealed by single molecule imaging.

Claudia N Buechner, Atanu Maiti, Alexander C Drohat, Ingrid Tessmer

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 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed.

  1. Article
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  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Alkyltransferase-like protein clusters scan DNA rapidly over long distances and recruit NER to alkyl-DNA lesions.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  15. Excision of 5-Carboxylcytosine by Thymine DNA Glycosylase.Journal of the American Chemical Society · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. Studying protein-DNA interactions using atomic force microscopy.Seminars in cell & developmental biology · 2018
    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

4 authors.

Claudia N BuechnerRudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
Atanu MaitiDepartment of Biochemistry and Molecular Biology and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Alexander C DrohatDepartment of Biochemistry and Molecular Biology and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ingrid TessmerRudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany ingrid.tessmer@virchow.uni-wuerzburg.de.

Funding

Structure and Mechanism of CpG specific DNA glycosylasesR01GM072711 · NIGMS · WADSWORTH CENTER · PI DROHAT, ALEX C · 2005 to 2020
$5.0M
NIGMS NIH HHS GM-72711NIGMS NIH HHS R01 GM072711
6 · The paper itself

Abstract

The ability of DNA glycosylases to rapidly and efficiently detect lesions among a vast excess of nondamaged DNA bases is vitally important in base excision repair (BER). Here, we use single molecule imaging by atomic force microscopy (AFM) supported by a 2-aminopurine fluorescence base flipping assay to study damage search by human thymine DNA glycosylase (hTDG), which initiates BER of mutagenic and cytotoxic G:T and G:U mispairs in DNA. Our data reveal an equilibrium between two conformational states of hTDG-DNA complexes, assigned as search complex (SC) and interrogation complex (IC), both at target lesions and undamaged DNA sites. Notably, for both hTDG and a second glycosylase, hOGG1, which recognizes structurally different 8-oxoguanine lesions, the conformation of the DNA in the SC mirrors innate structural properties of their respective target sites. In the IC, the DNA is sharply bent, as seen in crystal structures of hTDG lesion recognition complexes, which likely supports the base flipping required for lesion identification. Our results support a potentially general concept of sculpting of glycosylases to their targets, allowing them to exploit the energetic cost of DNA bending for initial lesion sensing, coupled with continuous (extrahelical) base interrogation during lesion search by DNA glycosylases.

Indexed as

DNA DamageDNA Repair2-AminopurineDNADNA GlycosylasesGuanineHumansMicroscopy, Atomic ForceMutationNucleic Acid ConformationSubstrate SpecificityThymine DNA Glycosylase2-Aminopurine8-hydroxyguanineDNADNA GlycosylasesGuanineoxoguanine glycosylase 1, humanThymine DNA Glycosylase

Identifiers

PMID25712093
PMCPMC4357730

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Registered trials

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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.