ArticleNucleic acids research2014
Critical role of DNA intercalation in enzyme-catalyzed nucleotide flipping.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Decoding the base flipping mechanism of the SET- and RING-associated (SRA) domain of the epigenetic UHRF1 protein.Nucleic acids research · 2025Article
- Structural basis of sequence-specific cytosine deamination by double-stranded DNA deaminase toxin DddA.Nature structural & molecular biology · 2023Article
- Computational investigations on target-site searching and recognition mechanisms by thymine DNA glycosylase during DNA repair process.Acta biochimica et biophysica Sinica · 2022Review
- Distinguishing Specific and Nonspecific Complexes of Alkyladenine DNA Glycosylase.Biochemistry · 2018Article
- Search for DNA damage by human alkyladenine DNA glycosylase involves early intercalation by an aromatic residue.The Journal of biological chemistry · 2017Article
- Mechanisms of glycosylase induced genomic instability.PloS one · 2017Article
- A Catalytic Role for C-H/π Interactions in Base Excision Repair by Bacillus cereus DNA Glycosylase AlkD.Journal of the American Chemical Society · 2016Article
- Repair of Alkylation Damage in Eukaryotic Chromatin Depends on Searching Ability of Alkyladenine DNA Glycosylase.ACS chemical biology · 2015Article
- Article
- Lesion search and recognition by thymine DNA glycosylase revealed by single molecule imaging.Nucleic acids research · 2015Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Nucleotide flipping is a common feature of DNA-modifying enzymes that allows access to target sites within duplex DNA. Structural studies have identified many intercalating amino acid side chains in a wide variety of enzymes, but the functional contribution of these intercalating residues is poorly understood. We used site-directed mutagenesis and transient kinetic approaches to dissect the energetic contribution of intercalation for human alkyladenine DNA glycosylase, an enzyme that initiates repair of alkylation damage. When AAG flips out a damaged nucleotide, the void in the duplex is filled by a conserved tyrosine (Y162). We find that tyrosine intercalation confers 140-fold stabilization of the extrahelical specific recognition complex, and that Y162 functions as a plug to slow the rate of unflipping by 6000-fold relative to the Y162A mutant. Surprisingly, mutation to the smaller alanine side chain increases the rate of nucleotide flipping by 50-fold relative to the wild-type enzyme. This provides evidence against the popular model that DNA intercalation accelerates nucleotide flipping. In the case of AAG, DNA intercalation contributes to the specific binding of a damaged nucleotide, but this enhanced specificity comes at the cost of reduced speed of nucleotide flipping.
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Registered trials
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.