2013
Conformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertion
Hohlbein J, Aigrain L, Craggs T, Bermek O, Potapova O, Shoolizadeh P, Grindley N, Joyce C, Kapanidis A. Conformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertion. Nature Communications 2013, 4: 2131. PMID: 23831915, PMCID: PMC3715850, DOI: 10.1038/ncomms3131.Peer-Reviewed Original ResearchConceptsClosed conformationDNA polymerase IIncorrect nucleotidesPolymerase ITernary complexSingle-molecule FRETActive site side chainsNucleotide selectionMutator phenotypeFidelity checkpointPrimary checkpointPhosphoryl transferFidelity mutantsConformational changesConformational landscapeDNA polymeraseNucleotide insertionConformational transitionDNA synthesisFRET valuesNucleotidesFree energy landscapeReduced affinityCheckpointConformation
2009
Conformational transitions in DNA polymerase I revealed by single-molecule FRET
Santoso Y, Joyce CM, Potapova O, Le Reste L, Hohlbein J, Torella JP, Grindley ND, Kapanidis AN. Conformational transitions in DNA polymerase I revealed by single-molecule FRET. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 107: 715-720. PMID: 20080740, PMCID: PMC2818957, DOI: 10.1073/pnas.0910909107.Peer-Reviewed Original ResearchConceptsDNA polymerase IClosed conformationPolymerase IConformational transitionSingle-molecule fluorescence resonance energy transferEarly stepsSingle-molecule FRETFluorescence resonance energy transferAvailable crystallographic structuresResonance energy transferMost DNA polymerasesComplementary ribonucleotidesChemical stepIncorrect substratesPolymerase moleculesPol DNAReaction pathwaysAcceptor fluorophoresKinetic checkpointsConformational dynamicsConformational flexibilityNucleotide additionStructural studiesDNA polymeraseCrystallographic structure
2008
Chemical shift mapping of γδ resolvase dimer and activated tetramer: Mechanistic implications for DNA strand exchange
Gehman J, Cocco M, Grindley N. Chemical shift mapping of γδ resolvase dimer and activated tetramer: Mechanistic implications for DNA strand exchange. Biochimica Et Biophysica Acta 2008, 1784: 2086-2092. PMID: 18840551, DOI: 10.1016/j.bbapap.2008.08.023.Peer-Reviewed Original ResearchConceptsDNA strand exchangeStrand exchangeChemical shift mappingWild-type dimerNMR chemical shift assignmentsChemical shift assignmentsDNA recombinaseResolvase dimersX-ray diffraction modelSequence regionsSubunit interfaceTetrameric stateProtomer-protomer interactionsGammadelta resolvaseShift mappingShift assignmentsMechanistic hypothesesStructural variationsResiduesFingers-Closing and Other Rapid Conformational Changes in DNA Polymerase I (Klenow Fragment) and Their Role in Nucleotide Selectivity
Joyce CM, Potapova O, DeLucia AM, Huang X, Basu VP, Grindley ND. Fingers-Closing and Other Rapid Conformational Changes in DNA Polymerase I (Klenow Fragment) and Their Role in Nucleotide Selectivity. Biochemistry 2008, 47: 6103-6116. PMID: 18473481, DOI: 10.1021/bi7021848.Peer-Reviewed Original Research
2007
Conformational Changes during Normal and Error-Prone Incorporation of Nucleotides by a Y-Family DNA Polymerase Detected by 2-Aminopurine Fluorescence †
DeLucia A, Grindley N, Joyce C. Conformational Changes during Normal and Error-Prone Incorporation of Nucleotides by a Y-Family DNA Polymerase Detected by 2-Aminopurine Fluorescence †. Biochemistry 2007, 46: 10790-10803. PMID: 17725324, DOI: 10.1021/bi7006756.Peer-Reviewed Original Research2-AminopurineArchaeal ProteinsBase Pair MismatchBase SequenceDeoxyribonucleotidesDNA Polymerase betaDNA Polymerase IDNA RepairDNA ReplicationDNA-Directed DNA PolymeraseFluorescent DyesFrameshift MutationModels, MolecularMolecular Sequence DataMutagenesis, InsertionalNucleic Acid ConformationSpectrometry, FluorescenceSubstrate SpecificitySulfolobusTemplates, Genetic
2006
The Properties of Steric Gate Mutants Reveal Different Constraints within the Active Sites of Y-family and A-family DNA Polymerases*
DeLucia A, Chaudhuri S, Potapova O, Grindley N, Joyce C. The Properties of Steric Gate Mutants Reveal Different Constraints within the Active Sites of Y-family and A-family DNA Polymerases*. Journal Of Biological Chemistry 2006, 281: 27286-27291. PMID: 16831866, DOI: 10.1074/jbc.m604393200.Peer-Reviewed Original ResearchMechanisms of Site-Specific Recombination*
Grindley ND, Whiteson KL, Rice PA. Mechanisms of Site-Specific Recombination*. Annual Review Of Biochemistry 2006, 75: 567-605. PMID: 16756503, DOI: 10.1146/annurev.biochem.73.011303.073908.Peer-Reviewed Original Research
2005
DNA Polymerase Catalysis in the Absence of Watson−Crick Hydrogen Bonds: Analysis by Single-Turnover Kinetics †
Potapova O, Chan C, DeLucia A, Helquist S, Kool E, Grindley N, Joyce C. DNA Polymerase Catalysis in the Absence of Watson−Crick Hydrogen Bonds: Analysis by Single-Turnover Kinetics †. Biochemistry 2005, 45: 890-898. PMID: 16411765, PMCID: PMC2567902, DOI: 10.1021/bi051792i.Peer-Reviewed Original ResearchStructure of a Synaptic γδ Resolvase Tetramer Covalently Linked to Two Cleaved DNAs
Li W, Kamtekar S, Xiong Y, Sarkis GJ, Grindley ND, Steitz TA. Structure of a Synaptic γδ Resolvase Tetramer Covalently Linked to Two Cleaved DNAs. Science 2005, 309: 1210-1215. PMID: 15994378, DOI: 10.1126/science.1112064.Peer-Reviewed Original Research
2003
The Architecture of the γδ Resolvase Crossover Site Synaptic Complex Revealed by Using Constrained DNA Substrates
Leschziner A, Grindley N. The Architecture of the γδ Resolvase Crossover Site Synaptic Complex Revealed by Using Constrained DNA Substrates. Molecular Cell 2003, 12: 775-781. PMID: 14527421, DOI: 10.1016/s1097-2765(03)00351-4.Peer-Reviewed Original ResearchUse of 2-Aminopurine Fluorescence To Examine Conformational Changes during Nucleotide Incorporation by DNA Polymerase I (Klenow Fragment) †
Purohit V, Grindley N, Joyce C. Use of 2-Aminopurine Fluorescence To Examine Conformational Changes during Nucleotide Incorporation by DNA Polymerase I (Klenow Fragment) †. Biochemistry 2003, 42: 10200-10211. PMID: 12939148, DOI: 10.1021/bi0341206.Peer-Reviewed Original Research
2001
A Model for the γδ Resolvase Synaptic Complex
Sarkis G, Murley L, Leschziner A, Boocock M, Stark W, Grindley N. A Model for the γδ Resolvase Synaptic Complex. Molecular Cell 2001, 8: 623-631. PMID: 11583624, DOI: 10.1016/s1097-2765(01)00334-3.Peer-Reviewed Original ResearchContacts between the 5′ Nuclease of DNA Polymerase I and Its DNA Substrate*
Xu Y, Potapova O, Leschziner A, Grindley N, Joyce C. Contacts between the 5′ Nuclease of DNA Polymerase I and Its DNA Substrate*. Journal Of Biological Chemistry 2001, 276: 30167-30177. PMID: 11349126, DOI: 10.1074/jbc.m100985200.Peer-Reviewed Original ResearchMeSH KeywordsArginineBase SequenceBinding SitesCircular DichroismDNADNA Polymerase IDNA RepairEscherichia coliKineticsLysineModels, ChemicalModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedMutationOrganophosphorus CompoundsPhosphatesProtein BindingProtein Structure, TertiarySubstrate SpecificityTemperatureTime FactorsConceptsDNA substratesDNA polymerase INuclease domainCleavage siteBasic residuesPolymerase IDuplex DNANuclease cleavagePhosphate ethylation interferenceDNA-binding regionActive site regionDNA replicationOne-half turnBacteriophage T5Eukaryotic nucleasesSubstrate bindingAbasic DNAEthylation interferenceDuplex portionHelical archNucleaseSite regionEscherichia coliMethylphosphonate substitutionsPrimer strand
1999
Mutants of Tn3 resolvase which do not require accessory binding sites for recombination activity
Arnold P, Blake D, Grindley N, Boocock M, Stark W. Mutants of Tn3 resolvase which do not require accessory binding sites for recombination activity. The EMBO Journal 1999, 18: 1407-1414. PMID: 10064606, PMCID: PMC1171230, DOI: 10.1093/emboj/18.5.1407.Peer-Reviewed Original Research
1998
Architecture of the γδ Resolvase Synaptosome Oriented Heterodimers Identify Interactions Essential for Synapsis and Recombination
Murley L, Grindley N. Architecture of the γδ Resolvase Synaptosome Oriented Heterodimers Identify Interactions Essential for Synapsis and Recombination. Cell 1998, 95: 553-562. PMID: 9827807, DOI: 10.1016/s0092-8674(00)81622-0.Peer-Reviewed Original ResearchHow E. coli DNA polymerase I (klenow fragment) distinguishes between deoxy- and dideoxynucleotides11Edited by A. R Fersht
Astatke M, Grindley N, Joyce C. How E. coli DNA polymerase I (klenow fragment) distinguishes between deoxy- and dideoxynucleotides11Edited by A. R Fersht. Journal Of Molecular Biology 1998, 278: 147-165. PMID: 9571040, DOI: 10.1006/jmbi.1998.1672.Peer-Reviewed Original ResearchConceptsMutant derivativesWild-type Klenow fragmentKlenow fragmentTernary complexAmino acid residuesE. coli DNA polymerase IIncorporation of dNTPsDNA polymerase IDNTP ternary complexPolymerase IAcid residuesPhosphoryl transferState kinetic parametersConformational changesNatural substratePositions 762DNA polymeraseEnzyme DNAKlenow fragment DNA polymeraseDNTPsIncoming dNTPDNTPSide chain resultsRibose moietyDideoxynucleotides
1995
Catalytic residues of gamma delta resolvase act in cis.
Boocock M, Zhu X, Grindley N. Catalytic residues of gamma delta resolvase act in cis. The EMBO Journal 1995, 14: 5129-5140. PMID: 7588641, PMCID: PMC394616, DOI: 10.1002/j.1460-2075.1995.tb00195.x.Peer-Reviewed Original ResearchBase SequenceBinding SitesCrossing Over, GeneticDNA NucleotidyltransferasesDNA Topoisomerases, Type IDNA Transposable ElementsGenetic Complementation TestModels, GeneticModels, MolecularMolecular Sequence DataPlasmidsRecombination, GeneticStructure-Activity RelationshipSubstrate SpecificityTransposasesDeoxynucleoside Triphosphate and Pyrophosphate Binding Sites in the Catalytically Competent Ternary Complex for the Polymerase Reaction Catalyzed by DNA Polymerase I (Klenow Fragment) (∗)
Astatke M, Grindley N, Joyce C. Deoxynucleoside Triphosphate and Pyrophosphate Binding Sites in the Catalytically Competent Ternary Complex for the Polymerase Reaction Catalyzed by DNA Polymerase I (Klenow Fragment) (∗). Journal Of Biological Chemistry 1995, 270: 1945-1954. PMID: 7829532, DOI: 10.1074/jbc.270.4.1945.Peer-Reviewed Original ResearchAmino Acid SequenceBacteriaBase SequenceBinding SitesConserved SequenceDeoxyribonucleotidesDiphosphatesDNA Polymerase IDNA PrimersKineticsMacromolecular SubstancesModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedOligodeoxyribonucleotidesPoint MutationPolymerase Chain ReactionProtein Structure, SecondarySaccharomyces cerevisiaeSequence Homology, Amino Acid
1993
Protein‐protein interactions directing resolvase site‐specific recombination: a structure‐function analysis.
Hughes R, Rice P, Steitz T, Grindley N. Protein‐protein interactions directing resolvase site‐specific recombination: a structure‐function analysis. The EMBO Journal 1993, 12: 1447-1458. PMID: 8385604, PMCID: PMC413356, DOI: 10.1002/j.1460-2075.1993.tb05788.x.Peer-Reviewed Original ResearchMapping interactions between the catalytic domain of resolvase and its DNA substrate using cysteine-coupled EDTA-iron.
Mazzarelli J, Ermácora M, Fox R, Grindley N. Mapping interactions between the catalytic domain of resolvase and its DNA substrate using cysteine-coupled EDTA-iron. Biochemistry 1993, 32: 2979-86. PMID: 8384484, DOI: 10.1021/bi00063a008.Peer-Reviewed Original Research