ArticleBiochemistry2011
The miscoding potential of 5-hydroxycytosine arises due to template instability in the replicative polymerase active site.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Dual cytosine modification through hydroxylation and arabinofuranosylation in phages.Nature chemical biology · 2026Article
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- Convenient syntheses of isotopically labeled pyrimidine 2'-deoxynucleosides and their 5-hydroxy oxidation products.Nucleosides, nucleotides & nucleic acids · 2025Article
- Error-Prone DNA Synthesis on Click-Ligated Templates.Doklady. Biochemistry and biophysics · 2024Article
- Comparison of mutation spectra induced by gamma-rays and carbon ion beams.Journal of radiation research · 2024Article
- Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin.Nucleic acids research · 2021Article
- Structure of New Binary and Ternary DNA Polymerase Complexes From Bacteriophage RB69.Frontiers in molecular biosciences · 2021Article
- Naturally occurring modified ribonucleosides.Wiley interdisciplinary reviews. RNA · 2020Review
- DNA Damage/Repair Management in Cancers.Cancers · 2020Review
- Mutational signatures of redox stress in yeast single-strand DNA and of aging in human mitochondrial DNA share a common feature.PLoS biology · 2019Article
- Molecular events during translocation and proofreading extracted from 200 static structures of DNA polymerase.Nucleic acids research · 2016Article
- Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Oxyl and hydroxyl radical transfer in mitochondrial amidoxime reducing component-catalyzed nitrite reduction.Journal of the American Chemical Society · 2015Article
- Looking for Waldo: a potential thermodynamic signature to DNA damage.Accounts of chemical research · 2014Article
- Oxidative stress-induced mutagenesis in single-strand DNA occurs primarily at cytosines and is DNA polymerase zeta-dependent only for adenines and guanines.Nucleic acids research · 2013Article
- Thermodynamic signature of DNA damage: characterization of DNA with a 5-hydroxy-2'-deoxycytidine·2'-deoxyguanosine base pair.Biochemistry · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
5-Hydroxycytosine (5-OHC) is a stable oxidation product of cytosine associated with an increased frequency of C → T transition mutations. When this lesion escapes recognition by the base excision repair pathway and persists to serve as a templating base during DNA synthesis, replicative DNA polymerases often misincorporate dAMP at the primer terminus, which can lead to fixation of mutations and subsequent disease. To characterize the dynamics of DNA synthesis opposite 5-OHC, we initiated a comparison of unmodified dCMP to 5-OHC, 5-fluorocytosine (5-FC), and 5-methylcytosine (5-MEC) in which these bases act as templates in the active site of RB69 gp43, a high-fidelity DNA polymerase sharing homology with human replicative DNA polymerases. This study presents the first crystal structure of any DNA polymerase binding this physiologically important premutagenic DNA lesion, showing that while dGMP is stabilized by 5-OHC through normal Watson-Crick base pairing, incorporation of dAMP leads to unstacking and instability in the template. Furthermore, the electronegativity of the C5 substituent appears to be important in the miscoding potential of these cytosine-like templates. While dAMP is incorporated opposite 5-OHC ~5 times more efficiently than opposite unmodified dCMP, an elevated level of incorporation is also observed opposite 5-FC but not 5-MEC. Taken together, these data imply that the nonuniform templating by 5-OHC is due to weakened stacking capabilities, which allows dAMP incorporation to proceed in a manner similar to that observed opposite abasic sites.
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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.