Nigel Grindley, PhD
Research & Publications
Biography
News
Research Summary
A unifying theme of our research is the study of enzymes that make and break phosphodiester bonds in DNA. Our research focuses on the detailed biochemical mechanisms of (i) site-specific recombination mediated by the prototypical serine recombinase, gd resolvase, and (ii) DNA synthesis and degradation mediated by the DNA polymerases Pol I (of E. coli), a highly accurate family A polymerase, and Dbh, an inaccurate family Y polymerase, which acts specifically to bypass damaged bases in the template strand during replication. In all three cases, we have detailed structural information obtained through collaborations with the X-ray crystallography group of Tom Steitz. In addition to using standard biochemical methods, we have recently added fluorescence techniques to dissect the biochemical pathways and define the nature and the role of the conformational transitions that take place during the processes of recombination or polymerase action.
Specialized Terms: Serine recombinases; site specific recombination; mechanisms of protein-DNA transactions; DNA polymerases
Extensive Research Description
Mechanisms of Protein-DNA transactions.
Our research group is
studying the mechanisms of a variety of enzymes that make, break, or
rearrange DNA. Our work involves a mixture of biochemistry and
genetics, and in several instances is strongly influenced by very
successful collaborations with the structure group of Tom Steitz.
Serine recombinases and site specific recombination.
Gamma-delta
resolvase is the prototype of a large family of site-specific
recombinases that use a specific serine residue as the nucleophile for
cutting and rejoining defined DNA segments. The serine recombinases
make concerted double strand breaks in the two recombination sites
before any exchange and resealing of DNA strands occurs. Phosphodiester
bond energy is conserved by formation of a covalent resolvase-DNA
(phospho-serine) linkage to the 5' ends of the transiently broken DNA
strands. Gamma-delta resolvase performs site-specific recombination in
an elaborate synaptic complex containing 12 resolvase subunits and two
114 base pair DNA segments (called res) each with three specific dimer
binding sites. We recently proposed a new model for the synaptic
complex, using a combination of structural information and a detailed
analysis of the various interactions between resolvase protomers that
are responsible for the assembly and function of the active complex. A
strong implication of the model is that the two crossover sites are on
the outside of the complex, well separated from one another. This
feature has been demonstrated both by biochemical studies and by a
recent crystal structure of a simplified resolvase synaptic complex
(four subunits with cleaved crossover sites) solved in the Steitz lab.
Current goals include testing implications of this synaptic structure
for strand exchange, and determining how this structure fits into the
full (12 subunit) synaptic complex.
Our goal is a structural and mechanistic understanding of the reactions involved in DNA replication, using simple DNA polymerases of known three-dimensional structure as model systems. Currently, we are exploring the basis of polymerase accuracy in two contrasting polymerases: the highly accurate DNA polymerase I of E. coli, and the very inaccurate Dbh lesion bypass polymerase. We are also using fluorescence techniques to define the nature and the role of the conformational transitions that take place during the polymerase reaction.
Coauthors
Research Interests
DNA; Molecular Biology; Poly(ADP-ribose) Polymerases
Selected Publications
- Duplication of an Insertion Sequence During Transpositional RecombinationWeinert T, Schaus N, Grindley N. Duplication of an Insertion Sequence During Transpositional Recombination. 2019, 365-377. DOI: 10.4324/9780429050329-29.
- Prechemistry Nucleotide Selection Checkpoints in the Reaction Pathway of DNA Polymerase I and Roles of Glu710 and Tyr766Bermek O, Grindley N, Joyce C. Prechemistry Nucleotide Selection Checkpoints in the Reaction Pathway of DNA Polymerase I and Roles of Glu710 and Tyr766. Biochemistry 2013, 52: 6258-6274. PMID: 23937394, PMCID: PMC3770053, DOI: 10.1021/bi400837k.
- Conformational landscapes of DNA polymerase I and mutator derivatives establish fidelity checkpoints for nucleotide insertionHohlbein 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.
- Remote control of DNA-acting enzymes by varying the Brownian dynamics of a distant DNA endBai H, Kath J, Zörgiebel F, Sun M, Ghosh P, Hatfull G, Grindley N, Marko J. Remote control of DNA-acting enzymes by varying the Brownian dynamics of a distant DNA end. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16546-16551. PMID: 23011800, PMCID: PMC3478594, DOI: 10.1073/pnas.1203118109.
- Remote Control of DNA-Acting Enzymes by Molecular Boundary ConditionsBai H, Kath J, Zorgebiel F, Grindley N, Marko J. Remote Control of DNA-Acting Enzymes by Molecular Boundary Conditions. Biophysical Journal 2012, 102: 70a. DOI: 10.1016/j.bpj.2011.11.412.
- Single-molecule analysis reveals the molecular bearing mechanism of DNA strand exchange by a serine recombinaseBai 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.
- Novel Conformational States in Mutator DNA Polymerases Observed Using Single-Molecule FRETHohlbein J, Joyce C, Shoolizadeh P, Evans G, Potapova O, Bermek O, Duchillumigusin D, Grindley N, Kapanidis A. Novel Conformational States in Mutator DNA Polymerases Observed Using Single-Molecule FRET. Biophysical Journal 2011, 100: 240a-241a. DOI: 10.1016/j.bpj.2010.12.1532.
- Distinct Roles of the Active-site Mg2+ Ligands, Asp882 and Asp705, of DNA Polymerase I (Klenow Fragment) during the Prechemistry Conformational Transitions*Bermek O, Grindley ND, Joyce CM. Distinct Roles of the Active-site Mg2+ Ligands, Asp882 and Asp705, of DNA Polymerase I (Klenow Fragment) during the Prechemistry Conformational Transitions*. Journal Of Biological Chemistry 2010, 286: 3755-3766. PMID: 21084297, PMCID: PMC3030377, DOI: 10.1074/jbc.m110.167593.
- Separating Static and Dynamic Heterogeneity in Single-Molecule FRET Experiments with Burst Variance Analysis (BVA)Torella J, Santoso Y, Holden S, Hohlbein J, Joyce C, Potapova O, Grindley N, Kapanidis A. Separating Static and Dynamic Heterogeneity in Single-Molecule FRET Experiments with Burst Variance Analysis (BVA). Biophysical Journal 2010, 98: 591a. DOI: 10.1016/j.bpj.2009.12.3213.
- Conformational Changes in DNA Polymerase I Revealed by Single-Molecule FRETSantoso Y, Joyce C, Potapova O, Le Reste L, Hohlbein J, Torella J, Grindley N, Kapanidis A. Conformational Changes in DNA Polymerase I Revealed by Single-Molecule FRET. Biophysical Journal 2010, 98: 436a-437a. DOI: 10.1016/j.bpj.2009.12.2370.
- Conformational transitions in DNA polymerase I revealed by single-molecule FRETSantoso 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.
- Single-molecule Study of Site-specific DNA Recombination by γδ ResolvaseSun M, Bai H, Grindley N, Marko J. Single-molecule Study of Site-specific DNA Recombination by γδ Resolvase. Biophysical Journal 2009, 96: 59a. DOI: 10.1016/j.bpj.2008.12.204.
- Chemical shift mapping of γδ resolvase dimer and activated tetramer: Mechanistic implications for DNA strand exchangeGehman 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.
- Fingers-Closing and Other Rapid Conformational Changes in DNA Polymerase I (Klenow Fragment) and Their Role in Nucleotide SelectivityJoyce 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.
- 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.
- The Movement of Tn 3 ‐Like Elements: Transposition and Cointegrate ResolutionGrindley N. The Movement of Tn 3 ‐Like Elements: Transposition and Cointegrate Resolution. 2007, 272-302. DOI: 10.1128/9781555817954.ch14.
- Implications of structures of synaptic tetramers of γδ resolvase for the mechanism of recombinationKamtekar S, Ho RS, Cocco MJ, Li W, Wenwieser SV, Boocock MR, Grindley ND, Steitz TA. Implications of structures of synaptic tetramers of γδ resolvase for the mechanism of recombination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 10642-10647. PMID: 16807292, PMCID: PMC1483221, DOI: 10.1073/pnas.0604062103.
- 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.
- Mechanisms 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.
- 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.
- Structure of a Synaptic γδ Resolvase Tetramer Covalently Linked to Two Cleaved DNAsLi 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.
- An Open Letter to Elias ZerhouniAltman S, Bassler BL, Beckwith J, Belfort M, Berg HC, Bloom B, Brenchley JE, Campbell A, Collier RJ, Connell N, Cozzarelli NR, Craig NL, Darst S, Ebright RH, Elledge SJ, Falkow S, Galan JE, Gottesman M, Gourse R, Grindley ND, Gross CA, Grossman A, Hochschild A, Howe M, Hurwitz J, Isberg RR, Kaplan S, Kornberg A, Kustu SG, Landick RC, Landy A, Levy SB, Losick R, Long SR, Maloy SR, Mekalanos JJ, Neidhardt FC, Pace NR, Ptashne M, Roberts JW, Roth JR, Rothman-Denes LB, Salyers A, Schaechter M, Shapiro L, Silhavy TJ, Simon MI, Walker G, Yanofsky C, Zinder N. An Open Letter to Elias Zerhouni. Science 2005, 307: 1409-1410. PMID: 15746409, DOI: 10.1126/science.307.5714.1409c.
- DNA Transposons: Different Proteins and Mechanisms but Similar RearrangementsDerbyshire K, Grindley N. DNA Transposons: Different Proteins and Mechanisms but Similar Rearrangements. 2004, 465-497. DOI: 10.1128/9781555817640.ch26.
- The Left End of IS2: a Compromise between Transpositional Activity and an Essential Promoter Function That Regulates the Transposition PathwayLewis L, Cylin E, Lee H, Saby R, Wong W, Grindley N. The Left End of IS2: a Compromise between Transpositional Activity and an Essential Promoter Function That Regulates the Transposition Pathway. Journal Of Bacteriology 2004, 186: 858-865. PMID: 14729714, PMCID: PMC321474, DOI: 10.1128/jb.186.3.858-865.2004.
- Robert M. MacnabGrindley N. Robert M. Macnab. Molecular Microbiology 2003, 51: 1-2. DOI: 10.1111/j.1365-2958.2004.03856.x.
- The Architecture of the γδ Resolvase Crossover Site Synaptic Complex Revealed by Using Constrained DNA SubstratesLeschziner 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.
- Use 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.
- An error‐prone family Y DNA polymerase (DinB homolog from Sulfolobus solfataricus) uses a ‘steric gate’ residue for discrimination against ribonucleotidesDeLucia A, Grindley N, Joyce C. An error‐prone family Y DNA polymerase (DinB homolog from Sulfolobus solfataricus) uses a ‘steric gate’ residue for discrimination against ribonucleotides. Nucleic Acids Research 2003, 31: 4129-4137. PMID: 12853630, PMCID: PMC165950, DOI: 10.1093/nar/gkg417.
- Interaction of DNA Polymerase I (Klenow Fragment) with the Single-Stranded Template beyond the Site of Synthesis †Turner R, Grindley N, Joyce C. Interaction of DNA Polymerase I (Klenow Fragment) with the Single-Stranded Template beyond the Site of Synthesis †. Biochemistry 2003, 42: 2373-2385. PMID: 12600204, DOI: 10.1021/bi026566c.
- The Mutational Specificity of the Dbh Lesion Bypass Polymerase and Its Implications*Potapova O, Grindley N, Joyce C. The Mutational Specificity of the Dbh Lesion Bypass Polymerase and Its Implications*. Journal Of Biological Chemistry 2002, 277: 28157-28166. PMID: 12023283, DOI: 10.1074/jbc.m202607200.
- Discrimination against purine–pyrimidine mispairs in the polymerase active site of DNA polymerase I: A structural explanationMinnick D, Liu L, Grindley N, Kunkel T, Joyce C. Discrimination against purine–pyrimidine mispairs in the polymerase active site of DNA polymerase I: A structural explanation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 1194-1199. PMID: 11830658, PMCID: PMC122166, DOI: 10.1073/pnas.032457899.
- Cryptic plasmids of Mycobacterium avium: Tn552 to the rescueKirby C, Waring A, Griffin T, Falkinham J, Grindley N, Derbyshire K. Cryptic plasmids of Mycobacterium avium: Tn552 to the rescue. Molecular Microbiology 2002, 43: 173-186. PMID: 11849545, DOI: 10.1046/j.1365-2958.2002.02729.x.
- The basis of asymmetry in IS2 transpositionLewis 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.
- A Model for the γδ Resolvase Synaptic ComplexSarkis 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.
- Contacts 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.
- In Vitro Transposition System for Efficient Generation of Random Mutants of Campylobacter jejuniColegio O, Griffin T, Grindley N, Galán J. In Vitro Transposition System for Efficient Generation of Random Mutants of Campylobacter jejuni. Journal Of Bacteriology 2001, 183: 2384-2388. PMID: 11244083, PMCID: PMC95150, DOI: 10.1128/jb.183.7.2384-2388.2001.
- DeletionGrindley N. Deletion. 2001, 295. DOI: 10.1016/b978-0-12-374984-0.00391-0.
- IntegrationGrindley N. Integration. 2001, 106. DOI: 10.1016/b978-0-12-374984-0.00803-2.
- Site-Specific RecombinationGrindley N. Site-Specific Recombination. 2001, 1842-1846. DOI: 10.1006/rwgn.2001.1200.
- Resolvase-Mediated DeletionGrindley N. Resolvase-Mediated Deletion. 2001, 1688-1692. DOI: 10.1006/rwgn.2001.1105.
- DeletionGrindley N. Deletion. 2001, 524. DOI: 10.1006/rwgn.2001.0317.
- IntegraseGrindley N. Integrase. 2001, 1038. DOI: 10.1006/rwgn.2001.0698.
- IntegrationGrindley N. Integration. 2001, 1041. DOI: 10.1006/rwgn.2001.0699.
- InversionGrindley N. Inversion. 2001, 1054. DOI: 10.1006/rwgn.2001.0711.
- ResolvaseGrindley N. Resolvase. 2001, 1687-1688. DOI: 10.1006/rwgn.2001.1104.
- Specialized RecombinationGrindley N. Specialized Recombination. 2001, 1857-1858. DOI: 10.1006/rwgn.2001.1215.
- TransposaseGrindley N. Transposase. 2001, 2033. DOI: 10.1006/rwgn.2001.1313.
- 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.
- Identification of Genes Encoding Exported Mycobacterium tuberculosis Proteins Using a Tn552′phoA In Vitro Transposition SystemBraunstein M, Griffin T, Kriakov J, Friedman S, Grindley N, Jacobs W. Identification of Genes Encoding Exported Mycobacterium tuberculosis Proteins Using a Tn552′phoA In Vitro Transposition System. Journal Of Bacteriology 2000, 182: 2732-2740. PMID: 10781540, PMCID: PMC101980, DOI: 10.1128/jb.182.10.2732-2740.2000.
- In vitro transposition of Tn552: A tool for DNA sequencing and mutagenesisGriffin T, Leschziner A, Grindley N, Parsons L, DeVost J, Derbyshire K. In vitro transposition of Tn552: A tool for DNA sequencing and mutagenesis. Nucleic Acids Research 1999, 27: 3859-3865. PMID: 10481025, PMCID: PMC148649, DOI: 10.1093/nar/27.19.3859.
- Mutants of Tn3 resolvase which do not require accessory binding sites for recombination activityArnold 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.
- Architecture of the γδ Resolvase Synaptosome Oriented Heterodimers Identify Interactions Essential for Synapsis and RecombinationMurley 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.
- Tn552 transposase catalyzes concerted strand transfer in vitroLeschziner A, Griffin T, Grindley N. Tn552 transposase catalyzes concerted strand transfer in vitro. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 7345-7350. PMID: 9636151, PMCID: PMC22612, DOI: 10.1073/pnas.95.13.7345.
- How E. coli DNA polymerase I (klenow fragment) distinguishes between deoxy- and dideoxynucleotides11Edited by A. R FershtAstatke 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.
- A single side chain prevents Escherichia coli DNA polymerase I (Klenow fragment) from incorporating ribonucleotidesAstatke 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.
- Site-specific recombination: Synapsis and strand exchange revealedGrindley N. Site-specific recombination: Synapsis and strand exchange revealed. Current Biology 1997, 7: r608-r612. PMID: 9368738, DOI: 10.1016/s0960-9822(06)00314-9.
- Two abundant intramolecular transposition products, resulting from reactions initiated at a single end, suggest that IS2 transposes by an unconventional pathwayLewis 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.
- Biochemical and mutational studies of the 5′-3′ exonuclease of DNA polymerase I of Escherichia coli11Edited by A. R. FershtXu 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.
- Cis preference of the IS 903 transposase is mediated by a combination of transposase instability and inefficient translationDerbyshire K, Grindley N. Cis preference of the IS 903 transposase is mediated by a combination of transposase instability and inefficient translation. Molecular Microbiology 1996, 21: 1261-1272. PMID: 8898394, DOI: 10.1111/j.1365-2958.1996.tb02587.x.
- DNA transposition: From a black box to a color monitorGrindley N, Leschziner A. DNA transposition: From a black box to a color monitor. Cell 1995, 83: 1063-1066. PMID: 8548793, DOI: 10.1016/0092-8674(95)90132-9.
- 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: 5129-40. PMID: 7588641, PMCID: PMC394616, DOI: 10.1002/j.1460-2075.1995.tb00195.x.
- A functional analysis of the inverted repeat of the γδ transposable elementMay E, Grindley N. A functional analysis of the inverted repeat of the γδ transposable element. Journal Of Molecular Biology 1995, 247: 578-587. DOI: 10.1016/s0022-2836(05)80139-1.
- The tyrosine‐6 hydroxyl of γδ resolvase is not required for the DNA cleavage and rejoining reactionsLeschziner A, Boocock M, Grindley N. The tyrosine‐6 hydroxyl of γδ resolvase is not required for the DNA cleavage and rejoining reactions. Molecular Microbiology 1995, 15: 865-870. PMID: 7596288, DOI: 10.1111/j.1365-2958.1995.tb02356.x.
- Deoxynucleoside 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.
- Resolvase-Mediated Site-Specific RecombinationGrindley N. Resolvase-Mediated Site-Specific Recombination. 1994, 8: 236-267. DOI: 10.1007/978-3-642-78666-2_14.
- Analysis of a Nucleoprotein Complex: the Synaptosome of γδ ResolvaseGrindley N. Analysis of a Nucleoprotein Complex: the Synaptosome of γδ Resolvase. Science 1993, 262: 738-740. PMID: 8235593, DOI: 10.1126/science.8235593.
- 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: 1447-58. PMID: 8385604, PMCID: PMC413356, DOI: 10.1002/j.1460-2075.1993.tb05788.x.
- Mapping 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.
- 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.
- Binding of the IS903 transposase to its inverted repeat in vitro.Derbyshire K, Grindley N. Binding of the IS903 transposase to its inverted repeat in vitro. The EMBO Journal 1992, 11: 3449-55. PMID: 1324175, PMCID: PMC556880, DOI: 10.1002/j.1460-2075.1992.tb05424.x.
- Side 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.
- Resolvase-catalysed reactions between res sites differing in the central dinucleotide of subsite I.Stark W, Grindley N, Hatfull G, Boocock M. Resolvase-catalysed reactions between res sites differing in the central dinucleotide of subsite I. The EMBO Journal 1991, 10: 3541-8. PMID: 1655422, PMCID: PMC453083, DOI: 10.1002/j.1460-2075.1991.tb04918.x.
- The Study of Protein-DNA Contacts by Ethylation InterferenceRimphanitchayakit V, Grindley N. The Study of Protein-DNA Contacts by Ethylation Interference. 1991, 111-120. DOI: 10.1007/978-3-0348-7561-5_9.
- Gamma delta transposase. Purification and analysis of its interaction with a transposon endWiater 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.
- The 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.
- Cooperativity mutants of the γδ resolvase identify an essential interdimer interactionHughes R, Hatfull G, Rice P, Steitz T, Grindley N. Cooperativity mutants of the γδ resolvase identify an essential interdimer interaction. Cell 1990, 63: 1331-1338. PMID: 2175679, DOI: 10.1016/0092-8674(90)90428-h.
- The crystal structure of the catalytic domain of the site-specific recombination enzyme γδ resolvase at 2.7 Å resolutionSanderson M, Freemont P, Rice P, Goldman A, Hatfull G, Grindley N, Steitz T. The crystal structure of the catalytic domain of the site-specific recombination enzyme γδ resolvase at 2.7 Å resolution. Cell 1990, 63: 1323-1329. PMID: 2175678, DOI: 10.1016/0092-8674(90)90427-g.
- 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.
- Uncoupling 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.
- Identification 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.
- The 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.
- Role of instability in the cis action of the insertion sequence IS903 transposase.Derbyshire K, Kramer M, Grindley N. Role of instability in the cis action of the insertion sequence IS903 transposase. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 4048-4052. PMID: 2161528, PMCID: PMC54044, DOI: 10.1073/pnas.87.11.4048.
- Saturation mutagenesis of the DNA site bound by the small carboxy-terminal domain of gamma delta resolvase.Rimphanitchayakit V, Grindley N. Saturation mutagenesis of the DNA site bound by the small carboxy-terminal domain of gamma delta resolvase. The EMBO Journal 1990, 9: 719-25. PMID: 2155779, PMCID: PMC551726, DOI: 10.1002/j.1460-2075.1990.tb08165.x.
- Preparation of heavy-atom derivatives using site-directed mutagenesis Introduction of cysteine residues into γδ resolvaseHatfull G, Sanderson M, Freemont P, Raccuia P, Grindley N, Steitz T. Preparation of heavy-atom derivatives using site-directed mutagenesis Introduction of cysteine residues into γδ resolvase. Journal Of Molecular Biology 1989, 208: 661-667. PMID: 2553982, DOI: 10.1016/0022-2836(89)90156-3.
- The 43 residue DNA binding domain of γδ resolvase binds adjacent major and minor grooves of DNARimphanitchayakit V, Halfull G, Grindley N. The 43 residue DNA binding domain of γδ resolvase binds adjacent major and minor grooves of DNA. Nucleic Acids Research 1989, 17: 1035-1050. PMID: 2537948, PMCID: PMC331720, DOI: 10.1093/nar/17.3.1035.
- The gamma delta resolvase bends the res site into a recombinogenic complex.Salvo J, Grindley N. The gamma delta resolvase bends the res site into a recombinogenic complex. The EMBO Journal 1988, 7: 3609-16. PMID: 2850169, PMCID: PMC454865, DOI: 10.1002/j.1460-2075.1988.tb03239.x.
- Gamma delta transposase and integration host factor bind cooperatively at both ends of gamma delta.Wiater L, Grindley N. Gamma delta transposase and integration host factor bind cooperatively at both ends of gamma delta. The EMBO Journal 1988, 7: 1907-11. PMID: 2844529, PMCID: PMC457184, DOI: 10.1002/j.1460-2075.1988.tb03024.x.
- Uncoupling of the recombination and topoisomerase activities of the γδ resolvase by a mutation at the crossover pointFalvey E, Hatfull G, Grindley N. Uncoupling of the recombination and topoisomerase activities of the γδ resolvase by a mutation at the crossover point. Nature 1988, 332: 861-863. PMID: 2833710, DOI: 10.1038/332861a0.
- 8 Transpositional and Site-Specific Recombination Mediated by Bacterial TransposonsGrindley N. 8 Transpositional and Site-Specific Recombination Mediated by Bacterial Transposons. 1988, 283-360. DOI: 10.1016/b978-0-12-456270-7.50013-8.
- Genetic analysis of the interaction of the insertion sequence IS903 transposase with its terminal inverted repeats.Derbyshire K, Hwang L, Grindley N. Genetic analysis of the interaction of the insertion sequence IS903 transposase with its terminal inverted repeats. Proceedings Of The National Academy Of Sciences Of The United States Of America 1987, 84: 8049-8053. PMID: 2825175, PMCID: PMC299474, DOI: 10.1073/pnas.84.22.8049.
- The γδ resolvase induces an unusual DNA structure at the recombinational crossover pointHatfull G, Noble S, Grindley N. The γδ resolvase induces an unusual DNA structure at the recombinational crossover point. Cell 1987, 49: 103-110. PMID: 3030563, DOI: 10.1016/0092-8674(87)90760-4.
- Contacts between gamma delta resolvase and the gamma delta res site.Falvey E, Grindley N. Contacts between gamma delta resolvase and the gamma delta res site. The EMBO Journal 1987, 6: 815-21. PMID: 3034611, PMCID: PMC553467, DOI: 10.1002/j.1460-2075.1987.tb04824.x.
- Helical phasing between DNA bends and the determination of bend directionSalvo J, Grindley N. Helical phasing between DNA bends and the determination of bend direction. Nucleic Acids Research 1987, 15: 9771-9779. PMID: 2827112, PMCID: PMC306530, DOI: 10.1093/nar/15.23.9771.
- Replicative and conservative transposition in bacteriaDerbyshire K, Grindley N. Replicative and conservative transposition in bacteria. Cell 1986, 47: 325-327. PMID: 3021339, DOI: 10.1016/0092-8674(86)90586-6.
- Analysis of gamma delta resolvase mutants in vitro: evidence for an interaction between serine-10 of resolvase and site I of res.Hatfull G, Grindley N. Analysis of gamma delta resolvase mutants in vitro: evidence for an interaction between serine-10 of resolvase and site I of res. Proceedings Of The National Academy Of Sciences Of The United States Of America 1986, 83: 5429-5433. PMID: 3016704, PMCID: PMC386300, DOI: 10.1073/pnas.83.15.5429.
- A simple and efficient procedure for saturation mutagenesis using mixed oligodeoxynucleotidesDerbyshire K, Salvo J, Grindley N. A simple and efficient procedure for saturation mutagenesis using mixed oligodeoxynucleotides. Gene 1986, 46: 145-152. PMID: 3803923, DOI: 10.1016/0378-1119(86)90398-7.
- Genetic mapping and DNA sequence analysis of mutations in the polA gene of Escherichia coliJoyce C, Fujii D, Laks H, Hughes C, Grindley N. Genetic mapping and DNA sequence analysis of mutations in the polA gene of Escherichia coli. Journal Of Molecular Biology 1985, 186: 283-293. PMID: 3910840, DOI: 10.1016/0022-2836(85)90105-6.
- Transpositional Recombination in ProkaryotesGrindley N, Reed R. Transpositional Recombination in Prokaryotes. Annual Review Of Biochemistry 1985, 54: 863-896. PMID: 2992361, DOI: 10.1146/annurev.bi.54.070185.004243.
- Analysis of the γδ res site Sites required for site-specific recombination and gene expressionWells R, Grindley N. Analysis of the γδ res site Sites required for site-specific recombination and gene expression. Journal Of Molecular Biology 1984, 179: 667-687. PMID: 6094833, DOI: 10.1016/0022-2836(84)90161-x.
- Mutants of the γδ resolvase: A genetic analysis of the recombination functionNewman B, Grindley N. Mutants of the γδ resolvase: A genetic analysis of the recombination function. Cell 1984, 38: 463-469. PMID: 6088082, DOI: 10.1016/0092-8674(84)90501-4.
- Method for determining whether a gene of Escherichia coli is essential: application to the polA gene.Joyce C, Grindley N. Method for determining whether a gene of Escherichia coli is essential: application to the polA gene. Journal Of Bacteriology 1984, 158: 636-43. PMID: 6233260, PMCID: PMC215477, DOI: 10.1128/jb.158.2.636-643.1984.
- Cleavage of the site-specific recombination protein gamma delta resolvase: the smaller of two fragments binds DNA specifically.Abdel-Meguid S, Grindley N, Templeton N, Steitz T. Cleavage of the site-specific recombination protein gamma delta resolvase: the smaller of two fragments binds DNA specifically. Proceedings Of The National Academy Of Sciences Of The United States Of America 1984, 81: 2001-2005. PMID: 6326096, PMCID: PMC345424, DOI: 10.1073/pnas.81.7.2001.
- Replicative and conservative transpositional recombination of insertion sequences.Weinert T, Derbyshire K, Hughson F, Grindley N. Replicative and conservative transpositional recombination of insertion sequences. Cold Spring Harbor Symposia On Quantitative Biology 1984, 49: 251-60. PMID: 6099240, DOI: 10.1101/sqb.1984.049.01.029.
- Insertion Sequence Duplication in Transpositional RecombinationWeinert T, Schaus N, Grindley N. Insertion Sequence Duplication in Transpositional Recombination. Science 1983, 222: 755-765. PMID: 6314502, DOI: 10.1126/science.6314502.
- Construction of a plasmid that overproduces the large proteolytic fragment (Klenow fragment) of DNA polymerase I of Escherichia coli.Joyce C, Grindley N. Construction of a plasmid that overproduces the large proteolytic fragment (Klenow fragment) of DNA polymerase I of Escherichia coli. Proceedings Of The National Academy Of Sciences Of The United States Of America 1983, 80: 1830-1834. PMID: 6340110, PMCID: PMC393703, DOI: 10.1073/pnas.80.7.1830.
- Transposition of Tn3 and related transposonsGrindley N. Transposition of Tn3 and related transposons. Cell 1983, 32: 3-5. PMID: 6297786, DOI: 10.1016/0092-8674(83)90490-7.
- Identification of two genes immediately downstream from the polA gene of Escherichia coli.Joyce C, Grindley N. Identification of two genes immediately downstream from the polA gene of Escherichia coli. Journal Of Bacteriology 1982, 152: 1211-9. PMID: 6183253, PMCID: PMC221628, DOI: 10.1128/jb.152.3.1211-1219.1982.
- Transposon-mediated site-specific recombination: Identification of three binding sites for resolvase at the res sites of γδ and Tn 3Grindley N, Lauth M, Wells R, Wityk R, Salvo J, Reed R. Transposon-mediated site-specific recombination: Identification of three binding sites for resolvase at the res sites of γδ and Tn 3. Cell 1982, 30: 19-27. PMID: 6290077, DOI: 10.1016/0092-8674(82)90007-1.
- Nucleotide sequence of the Escherichia coli polA gene and primary structure of DNA polymerase I.Joyce C, Kelley W, Grindley N. Nucleotide sequence of the Escherichia coli polA gene and primary structure of DNA polymerase I. Journal Of Biological Chemistry 1982, 257: 1958-1964. PMID: 6276402, DOI: 10.1016/s0021-9258(19)68132-9.
- Transposon-mediated site-specific recombination in vitro: DNA cleavage and protein-DNA linkage at the recombination siteReed R, Grindley N. Transposon-mediated site-specific recombination in vitro: DNA cleavage and protein-DNA linkage at the recombination site. Cell 1981, 25: 721-728. PMID: 6269756, DOI: 10.1016/0092-8674(81)90179-3.
- Analysis of the structure and function of the kanamycin-resistance transposon Tn903.Grindley N, Joyce C. Analysis of the structure and function of the kanamycin-resistance transposon Tn903. Cold Spring Harbor Symposia On Quantitative Biology 1981, 45 Pt 1: 125-33. PMID: 6271455, DOI: 10.1101/sqb.1981.045.01.021.
- Genetic and DNA sequence analysis of the kanamycin resistance transposon Tn903.Grindley N, Joyce C. Genetic and DNA sequence analysis of the kanamycin resistance transposon Tn903. Proceedings Of The National Academy Of Sciences Of The United States Of America 1980, 77: 7176-7180. PMID: 6261245, PMCID: PMC350464, DOI: 10.1073/pnas.77.12.7176.
- THE PRIMARY STRUCTURE OF DNA POLYMERASE I OF E. COLI11This work was supported by Health and Research Services Foundation grant V-34 (to NDFG), NIH grant GM24688 (to WSK) and ACS Faculty Research Award 198 (to WSK).Joyce C, Kelley W, Brown W, Grindley N. THE PRIMARY STRUCTURE OF DNA POLYMERASE I OF E. COLI11This work was supported by Health and Research Services Foundation grant V-34 (to NDFG), NIH grant GM24688 (to WSK) and ACS Faculty Research Award 198 (to WSK). 1980, 589-596. DOI: 10.1016/b978-0-12-048850-6.50054-5.
- Transposition of the Escherichia coli insertion element gamma generates a five-base-pair repeat.Reed RR, Young RA, Steitz JA, Grindley ND, Guyer MS. Transposition of the Escherichia coli insertion element gamma generates a five-base-pair repeat. Proceedings Of The National Academy Of Sciences Of The United States Of America 1979, 76: 4882-4886. PMID: 388421, PMCID: PMC413041, DOI: 10.1073/pnas.76.10.4882.
- INTEGRATION OF TRANSPOSABLE DNA ELEMENTS: ANALYSIS BY DNA SEQUENCING11This work was supported by grants from the National Science Foundation and the National Institutes of Health. GC holds a postdoctoral fellowship from Medical Research Council of Canada. A. I. B, holds a Career Development Award of the National Institutes of Health.Grindley N. INTEGRATION OF TRANSPOSABLE DNA ELEMENTS: ANALYSIS BY DNA SEQUENCING11This work was supported by grants from the National Science Foundation and the National Institutes of Health. GC holds a postdoctoral fellowship from Medical Research Council of Canada. A. I. B, holds a Career Development Award of the National Institutes of Health. 1979, 155-164. DOI: 10.1016/b978-0-12-198780-0.50016-7.
- IS1 insertion generates duplication of a nine base pair sequence at its target siteGrindley N. IS1 insertion generates duplication of a nine base pair sequence at its target site. Cell 1978, 13: 419-426. PMID: 350412, DOI: 10.1016/0092-8674(78)90316-1.
- polA6, a mutation affecting the DNA binding capacity of DNA polymerase IKelly W, Grindley N. polA6, a mutation affecting the DNA binding capacity of DNA polymerase I. Nucleic Acids Research 1976, 3: 2971-2984. PMID: 12497, PMCID: PMC343145, DOI: 10.1093/nar/3.11.2971.
- Mapping of thepolA locus ofEscherichia coli K12: Orientation of the amino- and carboxy-termini of the cistronKelley W, Grindley N. Mapping of thepolA locus ofEscherichia coli K12: Orientation of the amino- and carboxy-termini of the cistron. Molecular Genetics And Genomics 1976, 147: 307-314. PMID: 787765, DOI: 10.1007/bf00582882.
- Effects of different alleles of the E. coli K12 polA gene on the replication of non-transferring plasmidsGrindley N, Kelley W. Effects of different alleles of the E. coli K12 polA gene on the replication of non-transferring plasmids. Molecular Genetics And Genomics 1976, 143: 311-318. PMID: 765763, DOI: 10.1007/bf00269409.
- ErratumGrindley N, Kelley W. Erratum. Molecular Genetics And Genomics 1976, 145: 335-335. DOI: 10.1007/bf00325832.