2025
TblncRNA-23, a long non-coding RNA transcribed by RNA polymerase I, regulates developmental changes in Trypanosoma brucei
Galili-Kostin B, Rajan K, Ida Ashkenazi Y, Freedman A, Doniger T, Cohen-Chalamish S, Waldman Ben-Asher H, Unger R, Roditi I, Tschudi C, Michaeli S. TblncRNA-23, a long non-coding RNA transcribed by RNA polymerase I, regulates developmental changes in Trypanosoma brucei. Nature Communications 2025, 16: 3697. PMID: 40251171, PMCID: PMC12008373, DOI: 10.1038/s41467-025-58979-w.Peer-Reviewed Original ResearchConceptsProcyclic formsNon-coding RNAsLong non-coding RNAsPolycistronic transcription unitsRNA polymerase I.RNA polymerase IProtozoan parasite Trypanosoma bruceiRegulate gene expressionParasite Trypanosoma bruceiTsetse fly vectorComplex life cycleInsect midgutProcyclin genesSocial motilityLate procyclic formsRegulating developmental changesTranscription unitPolymerase I.Polymerase IBase pairsMammalian hostsTrypanosoma bruceiChanging abundanceInsect hostsTarget mRNAs
2024
A role for the kinetochore protein, NUF2, in ribosome biogenesis
brown T, Pichurin J, Parrado C, Kabeche L, Baserga S. A role for the kinetochore protein, NUF2, in ribosome biogenesis. Molecular Biology Of The Cell 2024, 36: ar16. PMID: 39705402, PMCID: PMC11809303, DOI: 10.1091/mbc.e24-08-0337.Peer-Reviewed Original ResearchConceptsPre-rRNA transcriptionNucleolar stress pathwayRibosome biogenesisPre-rRNASiRNA depletionSubunit of RNA polymerase IGenome-wide siRNA screenMCF10A human breast epithelial cellsRNA polymerase IHuman breast epithelial cellsBreast epithelial cellsKinetochore proteinsMitotic kinetochoresEukaryotic cellsPolymerase ISiRNA screenProtein partnersNUF2Sub-complexCell-based assaysProtein componentsRibosomeStress pathwaysTranscriptionProtein
2023
Nucleolar structure connects with global nuclear organization.
Wang C, Ma H, Baserga S, Pederson T, Huang S. Nucleolar structure connects with global nuclear organization. Molecular Biology Of The Cell 2023, 34: ar114. PMID: 37610836, PMCID: PMC10846622, DOI: 10.1091/mbc.e23-02-0062.Peer-Reviewed Original ResearchConceptsNucleolar structureGenomic lociNuclear domainsSpecific genomic lociGlobal nuclear organizationRNA processing factorsRNA polymerase ICajal bodiesNuclear organizationRibosome synthesisNuclear bodiesKnockdown cellsPerinucleolar compartmentPolymerase IIntranuclear locationHeLa cellsNucleolar segregationSpatial organizationNucleoliLociUtp4CellsRPA194SegregationCompositional changes
2022
Human pre-60S assembly factors link rRNA transcription to pre-rRNA processing
McCool M, Buhagiar A, Bryant C, Ogawa L, Abriola L, Surovtseva Y, Baserga S. Human pre-60S assembly factors link rRNA transcription to pre-rRNA processing. RNA 2022, 29: rna.079149.122. PMID: 36323459, PMCID: PMC9808572, DOI: 10.1261/rna.079149.122.Peer-Reviewed Original ResearchRRNA transcriptionRRNA processingRibosomal subunit biogenesisRNA polymerase IRibosome biosynthesisSubunit biogenesisRibosome biogenesisRibosome assemblyAssembly factorsTranscription controlBiogenesis factorsRRNA productionSteady-state levelsRNA transcriptionPolymerase IComplex membersHuman cellsProtein synthesisP53 stabilizationTranscriptionEssential processBiogenesisCell proliferationDual roleRegulatory details
2021
Increased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription
Ogawa LM, Buhagiar AF, Abriola L, Leland BA, Surovtseva YV, Baserga SJ. Increased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription. Molecular Biology Of The Cell 2021, 32: 956-973. PMID: 33689394, PMCID: PMC8108525, DOI: 10.1091/mbc.e20-10-0670.Peer-Reviewed Original ResearchConceptsRNA polymerase INumber of nucleoliRibosome biogenesisNucleolar organizer regionsPolymerase ICell cycleRNA polymerase I transcriptionPolymerase I transcriptionCell cycle regulationHigh-throughput quantitative imagingHuman diploid genomeIdentification of proteinsEukaryotic cellsG2/M phaseDiploid genomeNuclear condensatesRibosomal DNACycle regulationHuman breast epithelial cell lineBreast epithelial cell lineI transcriptionNovel regulatorEpithelial cell lineCycle progressionFunctional analysis
2013
Prechemistry Nucleotide Selection Checkpoints in the Reaction Pathway of DNA Polymerase I and Roles of Glu710 and Tyr766
Bermek 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.Peer-Reviewed Original ResearchConceptsFidelity checkpointDNA polymerase IPolymerase IHigh-fidelity DNA polymeraseMutator allelesCheckpoint functionMutator polymeraseIncorrect base pairsSelection checkpointDNA templateConformational changesSubstrate poolBase pairsDNA polymeraseComplementary nucleotidesCheckpointNoncomplementary nucleotidesTemplating baseFinger closingPolymeraseDNTPsNucleotidesCorrect incomingPathwayWeak bindingConformational 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
Fingers-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
2005
Autoantibody Recognition of Macromolecular Structures and Their Subunits
Champion E, Baserga S. Autoantibody Recognition of Macromolecular Structures and Their Subunits. 2005, 379-417. DOI: 10.1002/3527607854.ch17.Peer-Reviewed Original ResearchSm monoclonal antibodyRNA polymerase IBox C/D small nucleolar RNAsPre-mRNA splicingRNase MRPSmall nucleolar RNAsRNase PPolymerase IU3 snoRNASubcellular localizationMolecular markersProtein componentsNucleolar RNAsHuman exosomeNew functionsPolymyositis-scleroderma overlap syndromeCurrent understandingSnRNPsSnoRNAsSplicingFibrillarinNucleolarMonoclonal antibodiesExosomesHUBF
2001
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.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
The Tyr-265-to-Cys mutator mutant of DNA polymerase β induces a mutator phenotype in mouse LN12 cells
Clairmont C, Narayanan L, Sun K, Glazer P, Sweasy J. The Tyr-265-to-Cys mutator mutant of DNA polymerase β induces a mutator phenotype in mouse LN12 cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 9580-9585. PMID: 10449735, PMCID: PMC22251, DOI: 10.1073/pnas.96.17.9580.Peer-Reviewed Original ResearchConceptsMutator mutantsDNA polymerase betaTyr-265Mutator phenotypePolymerase betaWild-type DNA polymerase betaWild-type DNA polymeraseWild-type proteinBase excision repairRat DNA polymerase betaSpontaneous mutation frequencyDNA polymerase βDNA polymerase IMammalian cellsMutator polymeraseComplementation systemBeta mutantsExcision repairPolymerase IMutantsMutator activityGenetic instabilityHuman cellsPolymerase βEscherichia coli
1998
How 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
1997
A genetic system to identify DNA polymerase β mutator mutants
Washington S, Yoon M, Chagovetz A, Li S, Clairmont C, Preston B, Eckert K, Sweasy J. A genetic system to identify DNA polymerase β mutator mutants. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 1321-1326. PMID: 9037051, PMCID: PMC19789, DOI: 10.1073/pnas.94.4.1321.Peer-Reviewed Original ResearchConceptsMutator mutantsGenetic methodsPol betaDNA synthesisAccurate DNA synthesisDNA repair processesRat pol betaWild-type pol betaEscherichia coli DNA polymerase ISpontaneous mutation frequencyDNA polymerase IAltered fidelityDNA polymerase betaMutant proteinsDNA replicationGenetic systemMammalian cellsGenetic assaysPolymerase IMutantsDNA polymerase mutantsMutator activityPolymerase mutantsBeta enzymePolymerase beta
1996
Structure of Taq polymerase with DNA at the polymerase active site
Eom S, Wang J, Steitz T. Structure of Taq polymerase with DNA at the polymerase active site. Nature 1996, 382: 278-281. PMID: 8717047, DOI: 10.1038/382278a0.Peer-Reviewed Original ResearchConceptsDuplex DNADNA polymeraseEnded duplex DNAKlenow fragmentBlunt-end terminiActive-site cleftEscherichia coli DNA polymerase IProtein side chainsDNA polymerase ICo-crystal structurePolymerase active siteTaq polymeraseWide minor groovePol ICommon binding sitePolymerase IPolymerase domainExonuclease domainPolymerase cleftThermus aquaticusPolymeraseDNAPolymerase siteMinor grooveExonuclease site
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.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 reaction
1985
Genetic mapping and DNA sequence analysis of mutations in the polA gene of Escherichia coli
Joyce 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.Peer-Reviewed Original ResearchConceptsDNA sequence analysisDNA polymerase IThree-dimensional structurePolymerase ISequence analysisPolA geneSingle-subunit enzymeEscherichia coliEnzyme-DNA interactionsGenetic mappingDeletion mutantsSubunit enzymeMutant formsPrimary sequenceMutational changesBacteriophage lambdaExcellent modelPolA mutantsPolA mutationEnzymatic behaviorMutantsMutationsGenesDNAColi
1983
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.Peer-Reviewed Original ResearchConceptsDNA polymerase IOverproducing strainPolymerase IGene fusion techniquesLarge proteolytic fragmentCellular proteinsLac promoterGene fragmentsProtein structurePhage lambdaLeftward promoterEscherichia coliCarboxyl terminalPolymerase fragmentProteolytic fragmentsKlenow fragmentPromoterPlasmidPurification procedureFragmentsOverproductionExpressionI. MoreoverMechanistic studiesCloning
1982
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.Peer-Reviewed Original ResearchConceptsDNA polymerase IPolymerase INucleotide sequencePolA geneKilobase pair regionProtein chemical dataAmino acid sequenceWild-type alleleResidues 342Sequence comparisonDNA polymerase I.Polymerase moleculesDNA sequencesResidue 323Acid sequencePair regionPolA1 mutationPolymerase I.Primary structureBase pairsType alleleMild proteolysisGenesActive fragmentSequence
1980
Cold-sensitive regulatory mutants of simian virus 40
DiMaio D, Nathans D. Cold-sensitive regulatory mutants of simian virus 40. Journal Of Molecular Biology 1980, 140: 129-142. PMID: 6251230, DOI: 10.1016/0022-2836(80)90359-9.Peer-Reviewed Original ResearchConceptsRegulatory segmentBase substitutionsBglI siteWild-type plaquesProtein-coding sequencesProtein-nucleic acid interactionsCold-sensitive mutantsOrigin of replicationSet of mutantsSimian virus 40 mutantsDNA polymerase IBase substitution mutationsRNA processingRegulatory mutantsDNA replicationReplication originsViable mutantsSimian virus 40Small plaquesMutational alterationsWild-type virusPolymerase IMutantsRegulatory phenomenaSubstitution mutations
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