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
2011
Single-molecule analysis reveals the molecular bearing mechanism of DNA strand exchange by a serine recombinase
Bai H, Sun M, Ghosh P, Hatfull GF, Grindley ND, Marko JF. Single-molecule analysis reveals the molecular bearing mechanism of DNA strand exchange by a serine recombinase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 7419-7424. PMID: 21502527, PMCID: PMC3088605, DOI: 10.1073/pnas.1018436108.Peer-Reviewed Original ResearchMeSH KeywordsBiotinDigoxigeninDNA NucleotidyltransferasesDNA, SuperhelicalEscherichia coliPlasmidsRotationSerine
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
2001
The basis of asymmetry in IS2 transposition
Lewis L, Gadura N, Greene M, Saby R, Grindley N. The basis of asymmetry in IS2 transposition. Molecular Microbiology 2001, 42: 887-901. PMID: 11737634, DOI: 10.1046/j.1365-2958.2001.02662.x.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
2000
Coordination between the Polymerase and 5′-Nuclease Components of DNA Polymerase I of Escherichia coli *
Xu Y, Grindley N, Joyce C. Coordination between the Polymerase and 5′-Nuclease Components of DNA Polymerase I of Escherichia coli *. Journal Of Biological Chemistry 2000, 275: 20949-20955. PMID: 10806216, DOI: 10.1074/jbc.m909135199.Peer-Reviewed Original Research
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 moietyDideoxynucleotidesA single side chain prevents Escherichia coli DNA polymerase I (Klenow fragment) from incorporating ribonucleotides
Astatke M, Ng K, Grindley N, Joyce C. A single side chain prevents Escherichia coli DNA polymerase I (Klenow fragment) from incorporating ribonucleotides. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 3402-3407. PMID: 9520378, PMCID: PMC19848, DOI: 10.1073/pnas.95.7.3402.Peer-Reviewed Original Research
1997
Two abundant intramolecular transposition products, resulting from reactions initiated at a single end, suggest that IS2 transposes by an unconventional pathway
Lewis L, Grindley N. Two abundant intramolecular transposition products, resulting from reactions initiated at a single end, suggest that IS2 transposes by an unconventional pathway. Molecular Microbiology 1997, 25: 517-529. PMID: 9302014, DOI: 10.1046/j.1365-2958.1997.4871848.x.Peer-Reviewed Original ResearchBacterial ProteinsBase SequenceBinding SitesCloning, MolecularDNA NucleotidyltransferasesDNA PrimersDNA Transposable ElementsDNA, BacterialDNA, CircularEscherichia coliEscherichia coli ProteinsMicroscopy, ElectronModels, GeneticMolecular Sequence DataNucleic Acid ConformationPolymerase Chain ReactionRecombinant Fusion ProteinsTransposasesBiochemical and mutational studies of the 5′-3′ exonuclease of DNA polymerase I of Escherichia coli11Edited by A. R. Fersht
Xu Y, Derbyshire V, Ng K, Sun X, Grindley N, Joyce C. Biochemical and mutational studies of the 5′-3′ exonuclease of DNA polymerase I of Escherichia coli11Edited by A. R. Fersht. Journal Of Molecular Biology 1997, 268: 284-302. PMID: 9159471, DOI: 10.1006/jmbi.1997.0967.Peer-Reviewed Original Research
1992
Reactions at the polymerase active site that contribute to the fidelity of Escherichia coli DNA polymerase I (Klenow fragment).
Joyce C, Sun X, Grindley N. Reactions at the polymerase active site that contribute to the fidelity of Escherichia coli DNA polymerase I (Klenow fragment). Journal Of Biological Chemistry 1992, 267: 24485-24500. PMID: 1447195, DOI: 10.1016/s0021-9258(18)35792-2.Peer-Reviewed Original ResearchSide chains involved in catalysis of the polymerase reaction of DNA polymerase I from Escherichia coli.
Polesky A, Dahlberg M, Benkovic S, Grindley N, Joyce C. Side chains involved in catalysis of the polymerase reaction of DNA polymerase I from Escherichia coli. Journal Of Biological Chemistry 1992, 267: 8417-8428. PMID: 1569092, DOI: 10.1016/s0021-9258(18)42461-1.Peer-Reviewed Original Research
1991
Gamma delta transposase. Purification and analysis of its interaction with a transposon end
Wiater L, Grindley N. Gamma delta transposase. Purification and analysis of its interaction with a transposon end. Journal Of Biological Chemistry 1991, 266: 1841-1849. PMID: 1846366, DOI: 10.1016/s0021-9258(18)52370-x.Peer-Reviewed Original ResearchThe 3′‐5′ exonuclease of DNA polymerase I of Escherichia coli: contribution of each amino acid at the active site to the reaction.
Derbyshire V, Grindley N, Joyce C. The 3′‐5′ exonuclease of DNA polymerase I of Escherichia coli: contribution of each amino acid at the active site to the reaction. The EMBO Journal 1991, 10: 17-24. PMID: 1989882, PMCID: PMC452606, DOI: 10.1002/j.1460-2075.1991.tb07916.x.Peer-Reviewed Original ResearchConceptsActive siteMetal ionsEnzyme-bound metal ionSide chainsExonuclease reactionDivalent metal ionsAmino acid side chainsCarboxylate side chainAcid side chainsHydroxide ionMetal ligandsNucleophilic attackIonsTerminal phosphodiester bondPhosphodiester bondReactionExonuclease active siteActivity resultsKlenow fragmentDuplex DNA substratesCatalysisChainCarboxylateTerminal baseSubstrate
1990
Integration host factor increases the transpositional immunity conferred by gamma delta ends
Wiater L, Grindley N. Integration host factor increases the transpositional immunity conferred by gamma delta ends. Journal Of Bacteriology 1990, 172: 4951-4958. PMID: 2168370, PMCID: PMC213150, DOI: 10.1128/jb.172.9.4951-4958.1990.Peer-Reviewed Original ResearchUncoupling of transpositional immunity from gamma delta transposition by a mutation at the end of gamma delta
Wiater L, Grindley N. Uncoupling of transpositional immunity from gamma delta transposition by a mutation at the end of gamma delta. Journal Of Bacteriology 1990, 172: 4959-4963. PMID: 2168371, PMCID: PMC213151, DOI: 10.1128/jb.172.9.4959-4963.1990.Peer-Reviewed Original ResearchIdentification of residues critical for the polymerase activity of the Klenow fragment of DNA polymerase I from Escherichia coli.
Polesky A, Steitz T, Grindley N, Joyce C. Identification of residues critical for the polymerase activity of the Klenow fragment of DNA polymerase I from Escherichia coli. Journal Of Biological Chemistry 1990, 265: 14579-14591. PMID: 2201688, DOI: 10.1016/s0021-9258(18)77342-0.Peer-Reviewed Original ResearchConceptsCluster of residuesIdentification of residuesSite-directed mutagenesisActive site residuesAmino acid residuesFuture mutational studiesImportant active site residuesDNA-binding propertiesActive site regionDNA polymerase IGenetic screenPosition 849Polymerase active siteMutant proteinsDNA substratesMutational studiesPolymerase IBiochemical experimentsSite residuesAcid residuesSite regionEscherichia coliPolymerase activityMutationsPolymerase reactionThe two functional domains of gamma delta resolvase act on the same recombination site: implications for the mechanism of strand exchange.
Dröge P, Hatfull G, Grindley N, Cozzarelli N. The two functional domains of gamma delta resolvase act on the same recombination site: implications for the mechanism of strand exchange. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 5336-5340. PMID: 2164677, PMCID: PMC54318, DOI: 10.1073/pnas.87.14.5336.Peer-Reviewed Original ResearchConceptsDNA-protein complexesRecombination sitesSite-specific recombinationGamma delta resolvaseDNA exchangeCatalytic domainStrand exchangeFunctional domainsResolvaseResolvase subunitsDNA strandsRes sitesSynaptic complexDNAStrand breakageRecombinationReunion eventDomainSitesComplexesSubunitsStrandsBreakageSynaptosomes