ArticleBiophysical journal2007
Differing conformational pathways before and after chemistry for insertion of dATP versus dCTP opposite 8-oxoG in DNA polymerase beta.
Article in Biophysical journal, 2007. 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, 23 citations in OpenAlex.
- Review
- Insertion of oxidized nucleotide triggers rapid DNA polymerase opening.Nucleic acids research · 2016Article
- Reprint of "Oxidant and environmental toxicant-induced effects compromise DNA ligation during base excision DNA repair".DNA repair · 2015Review
- Oxidant and environmental toxicant-induced effects compromise DNA ligation during base excision DNA repair.DNA repair · 2015Review
- Optimal and variant metal-ion routes in DNA polymerase β's conformational pathways.Journal of the American Chemical Society · 2014Article
- How DNA polymerase X preferentially accommodates incoming dATP opposite 8-oxoguanine on the template.Biophysical journal · 2013Article
- DNA polymerase minor groove interactions modulate mutagenic bypass of a templating 8-oxoguanine lesion.Nucleic acids research · 2013Article
- "Gate-keeper" residues and active-site rearrangements in DNA polymerase μ help discriminate non-cognate nucleotides.PLoS computational biology · 2013Article
- Molecular dynamics simulations of double-stranded DNA in an explicit solvent model with the zero-dipole summation method.PloS one · 2013Article
- Catalytic effects of mutations of distant protein residues in human DNA polymerase β: theory and experiment.Biochemistry · 2012Article
- Perspective: pre-chemistry conformational changes in DNA polymerase mechanisms.Theoretical chemistry accounts · 2012Article
- DNA polymerase family X: function, structure, and cellular roles.Biochimica et biophysica acta · 2010Review
- Mismatched base-pair simulations for ASFV Pol X/DNA complexes help interpret frequent G*G misincorporation.Journal of molecular biology · 2008Article
- Article
- The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine.Human molecular genetics · 2007Article
- Distinct energetics and closing pathways for DNA polymerase beta with 8-oxoG template and different incoming nucleotides.BMC structural biology · 2007Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
To elucidate how human DNA polymerase beta (pol beta) discriminates dATP from dCTP when processing 8-oxoguanine (8-oxoG), we analyze a series of dynamics simulations before and after the chemical step with dATP and dCTP opposite an 8-oxoG template started from partially open complexes of pol beta. Analyses reveal that the thumb closing of pol beta before chemistry is hampered when the incorrect nucleotide dATP is bound opposite 8-oxoG; the unfavorable interaction between active-site residue Tyr(271) and dATP that causes an anti to syn change in the 8-oxoG (syn):dATP complex explains this slow motion, in contrast to the 8-oxoG (anti):dCTP system. Such differences in conformational pathways before chemistry for mismatched versus matched complexes help explain the preference for correct insertion across 8-oxoG by pol beta. Together with reference studies with a nonlesioned G template, we propose that 8-oxoG leads to lower efficiency in pol beta's incorporation of dCTP compared with G by affecting the requisite active-site geometry for the chemical reaction before chemistry. Furthermore, because the active site is far from ready for the chemical reaction after partial closing or even full thumb closing, we suggest that pol beta is tightly controlled not only by the chemical step but also by a closely related requirement for subtle active-site rearrangements after thumb movement but before chemistry.
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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.