ArticleBiochemistry2010
Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP and dGMP to be inserted opposite Guanidinohydantoin .
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Products of Oxidative Guanine Damage Form Base Pairs with Guanine.International journal of molecular sciences · 2020Review
- RNA polymerase II stalls on oxidative DNA damage via a torsion-latch mechanism involving lone pair-π and CH-π interactions.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Nanopore Analysis of the 5-Guanidinohydantoin to Iminoallantoin Isomerization in Duplex DNA.The Journal of organic chemistry · 2018Article
- Generation, repair and replication of guanine oxidation products.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2017Review
- pH-Dependent Equilibrium between 5-Guanidinohydantoin and Iminoallantoin Affects Nucleotide Insertion Opposite the DNA Lesion.The Journal of organic chemistry · 2016Article
- RB69 DNA polymerase structure, kinetics, and fidelity.Biochemistry · 2014Review
- Crystal structure of DNA polymerase β with DNA containing the base lesion spiroiminodihydantoin in a templating position.Biochemistry · 2014Article
- Article
- How DNA polymerase X preferentially accommodates incoming dATP opposite 8-oxoguanine on the template.Biophysical journal · 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
- Calculation of the stabilization energies of oxidatively damaged guanine base pairs with guanine.Molecules (Basel, Switzerland) · 2012Article
- Structural insights into complete metal ion coordination from ternary complexes of B family RB69 DNA polymerase.Biochemistry · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Continuous oxidative damage inflicted on DNA produces 7,8-dihydro-8-oxoguanine (8-oxoG), a commonly occurring lesion that can potentially cause cancer by producing G → T transversions during DNA replication. Mild oxidation of 8-oxoG leads to the formation of hydantoins, specifically guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp), which are 100% mutagenic because they encode almost exclusively the insertion of dAMP and dGMP (encoding G → T and G → C transversions, respectively). The wild-type (wt) pol α family DNA polymerase from bacteriophage RB69 (RB69pol) inserts dAMP and dGMP with low efficiency when situated opposite Gh. In contrast, the RB69pol Y567A mutant inserts both of these dNMPs opposite Gh with >100-fold higher efficiency than wt. We now report the crystal structure of the "closed" preinsertion complex for the Y567A mutant with dATP opposite a templating Gh (R-configuration) in a 13/18mer primer-template (P/T) at 2.0 Å resolution. The structure data reveal that the Y to A substitution provides the nascent base pair binding pocket (NBP) with the flexibility to accommodate Gh by allowing G568 to move in the major-to-minor groove direction of the P/T. Thus, Gh is rejected as a templating base by wt RB69pol because G568 is inflexible, preventing Gh from pairing with the incoming dATP or dGTP base.
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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.