ArticleJournal of molecular biology2011
A crystallographic study of the role of sequence context in thymine glycol bypass by a replicative DNA polymerase serendipitously sheds light on the exonuclease complex.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- A unified catalytic mechanism in bifunctional DNA glycosylases with an evolutionarily conserved aspartate-lysine dyad.Nature communications · 2026Article
- A steric gate prevents mutagenic dATP incorporation opposite 8-oxo-deoxyguanosine in mitochondrial DNA polymerases.The FEBS journal · 2025Article
- Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities.Nucleic acids research · 2022Article
- Dynamics of 5R-Tg Base Flipping in DNA Duplexes Based on Simulations─Agreement with Experiments and Beyond.Journal of chemical information and modeling · 2022Article
- Structure of New Binary and Ternary DNA Polymerase Complexes From Bacteriophage RB69.Frontiers in molecular biosciences · 2021Article
- Insights into DNA polymerase δ's mechanism for accurate DNA replication.Journal of molecular modeling · 2019Article
- In Vitro Bypass of Thymidine Glycol by DNA Polymerase θ Forms Sequence-Dependent Frameshift Mutations.Biochemistry · 2017Article
- Molecular events during translocation and proofreading extracted from 200 static structures of DNA polymerase.Nucleic acids research · 2016Article
- Polymerase and exonuclease activities in herpes simplex virus type 1 DNA polymerase are not highly coordinated.Biochemistry · 2015Article
- Article
- Structural insights into eukaryotic DNA replication.Frontiers in microbiology · 2014Review
- DNA polymerase hybrids derived from the family-B enzymes of Pyrococcus furiosus and Thermococcus kodakarensis: improving performance in the polymerase chain reaction.Frontiers in microbiology · 2014Article
- The RECQL4 protein, deficient in Rothmund-Thomson syndrome is active on telomeric D-loops containing DNA metabolism blocking lesions.DNA repair · 2013Article
- Human DNA polymerase β, but not λ, can bypass a 2-deoxyribonolactone lesion together with proliferating cell nuclear antigen.ACS chemical biology · 2013Article
- Unwinding of primer-templates by archaeal family-B DNA polymerases in response to template-strand uracil.Nucleic acids research · 2013Article
- Utility of the bacteriophage RB69 polymerase gp43 as a surrogate enzyme for herpesvirus orthologs.Viruses · 2013Review
- Structural characterization of viral ortholog of human DNA glycosylase NEIL1 bound to thymine glycol or 5-hydroxyuracil-containing DNA.The Journal of biological chemistry · 2012Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Thymine glycol (Tg) is the most common oxidation product of thymine and is known to be a strong block to replicative DNA polymerases. A previously solved structure of the bacteriophage RB69 DNA polymerase (RB69 gp43) in complex with Tg in the sequence context 5'-G-Tg-G shed light on how Tg blocks primer elongation: The protruding methyl group of the oxidized thymine displaces the adjacent 5'-G, which can no longer serve as a template for primer elongation [Aller, P., Rould, M. A., Hogg, M, Wallace, S. S. & Doublié S. (2007). A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycol. Proc. Natl. Acad. Sci. USA, 104, 814-818.]. Several studies showed that in the sequence context 5'-C-Tg-purine, Tg is more likely to be bypassed by Klenow fragment, an A-family DNA polymerase. We set out to investigate the role of sequence context in Tg bypass in a B-family polymerase and to solve the crystal structures of the bacteriophage RB69 DNA polymerase in complex with Tg-containing DNA in the three remaining sequence contexts: 5'-A-Tg-G, 5'-T-Tg-G, and 5'-C-Tg-G. A combination of several factors-including the associated exonuclease activity, the nature of the 3' and 5' bases surrounding Tg, and the cis-trans interconversion of Tg-influences Tg bypass. We also visualized for the first time the structure of a well-ordered exonuclease complex, allowing us to identify and confirm the role of key residues (Phe123, Met256, and Tyr257) in strand separation and in the stabilization of the primer strand in the exonuclease site.
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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.