ArticleBiochemistry2010
Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP to be inserted opposite 7,8-dihydro-8-oxoguanine .
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Structural basis of transcription-coupled RNA damage by incorporation of oxidized ribonucleotides.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Transcription-Coupled Template Reconfiguration of 8-Oxoguanine for Error-Prone Transcription Revealed by Time-Resolved X-ray Crystallography and Molecular Dynamics.Journal of the American Chemical Society · 2025Article
- Article
- The use of modified and non-natural nucleotides provide unique insights into pro-mutagenic replication catalyzed by polymerase eta.Nucleic acids research · 2016Article
- RB69 DNA polymerase structure, kinetics, and fidelity.Biochemistry · 2014Review
- Structural characterization of a mouse ortholog of human NEIL3 with a marked preference for single-stranded DNA.Structure (London, England : 1993) · 2013Article
- DNA polymerase minor groove interactions modulate mutagenic bypass of a templating 8-oxoguanine lesion.Nucleic acids research · 2013Article
- Using a fluorescent cytosine analogue tC(o) to probe the effect of the Y567 to Ala substitution on the preinsertion steps of dNMP incorporation by RB69 DNA polymerase.Biochemistry · 2012Article
- Binary complex crystal structure of DNA polymerase β reveals multiple conformations of the templating 8-oxoguanine lesion.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- The miscoding potential of 5-hydroxycytosine arises due to template instability in the replicative polymerase active site.Biochemistry · 2011Article
- Structure of the 2-aminopurine-cytosine base pair formed in the polymerase active site of the RB69 Y567A-DNA polymerase.Biochemistry · 2011Article
- Structural insights into complete metal ion coordination from ternary complexes of B family RB69 DNA polymerase.Biochemistry · 2011Article
- DNA polymerases provide a canon of strategies for translesion synthesis past oxidatively generated lesions.Current opinion in structural biology · 2011Review
- DNA polymerase structure-based insight on the mutagenic properties of 8-oxoguanine.Mutation research · 2010Review
- Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP and dGMP to be inserted opposite Guanidinohydantoin .Biochemistry · 2010Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Accurate copying of the genome by DNA polymerases is challenging due in part to the continuous damage inflicted on DNA, which results from its contact with reactive oxygen species (ROS), producing lesions such as 7,8-dihydro-8-oxoguanine (8-oxoG). The deleterious effects of 8-oxoG can be attributed to its dual coding potential that leads to G --> T transversions. The wild-type (wt) pol alpha family DNA polymerase from bacteriophage RB69 (RB69pol) prefers to insert dCMP as opposed to dAMP when situated opposite 8-oxoG by >2 orders of magnitude as demonstrated using pre-steady-state kinetics (k(pol)/K(d,app)). In contrast, the Y567A mutant of RB69pol inserts both dCMP and dAMP opposite 8-oxoG rapidly and with equal efficiency. We have determined the structures of preinsertion complexes for the Y567A mutant with dATP and dCTP opposite a templating 8-oxoG in a 13/18mer primer-template (P/T) at resolutions of 2.3 and 2.1 A, respectively. Our structures show that the 8-oxoG residue is in the anti conformation when paired opposite dCTP, but it flips to a syn conformation forming a Hoogstein base pair with an incoming dATP. Although the Y567A substitution does not significantly change the volume of the pocket occupied by anti-8-oxoG, it does provide residue G568 the flexibility to move deeper into the minor groove of the P/T to accommodate, and stabilize, syn-8-oxoG. These results support the hypothesis that it is the flexibility of the nascent base pair binding pocket (NBP) in the Y567A mutant that allows efficient insertion of dAMP opposite 8-oxoG.
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