2017
Defective Nucleotide Release by DNA Polymerase β Mutator Variant E288K Is the Basis of Its Low Fidelity
Mahmoud MM, Schechter A, Alnajjar KS, Huang J, Towle-Weicksel J, Eckenroth BE, Doublié S, Sweasy JB. Defective Nucleotide Release by DNA Polymerase β Mutator Variant E288K Is the Basis of Its Low Fidelity. Biochemistry 2017, 56: 5550-5559. PMID: 28945359, PMCID: PMC5654646, DOI: 10.1021/acs.biochem.7b00869.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionBiocatalysisColonic NeoplasmsDNADNA Polymerase betaDNA RepairDNA ReplicationEnzyme StabilityFluorescent DyesHumansKineticsModels, MolecularMutagenesis, Site-DirectedMutationNaphthalenesulfonatesNeoplasm ProteinsP-DimethylaminoazobenzeneProtein ConformationProtein Interaction Domains and MotifsProtein RefoldingRecombinant ProteinsSubstrate SpecificityDNA Polymerase β Cancer-Associated Variant I260M Exhibits Nonspecific Selectivity toward the β–γ Bridging Group of the Incoming dNTP
Alnajjar KS, Negahbani A, Nakhjiri M, Krylov IS, Kashemirov BA, McKenna CE, Goodman MF, Sweasy JB. DNA Polymerase β Cancer-Associated Variant I260M Exhibits Nonspecific Selectivity toward the β–γ Bridging Group of the Incoming dNTP. Biochemistry 2017, 56: 5449-5456. PMID: 28862868, PMCID: PMC5634933, DOI: 10.1021/acs.biochem.7b00713.Peer-Reviewed Original ResearchA Change in the Rate-Determining Step of Polymerization by the K289M DNA Polymerase β Cancer-Associated Variant
Alnajjar KS, Garcia-Barboza B, Negahbani A, Nakhjiri M, Kashemirov B, McKenna C, Goodman MF, Sweasy JB. A Change in the Rate-Determining Step of Polymerization by the K289M DNA Polymerase β Cancer-Associated Variant. Biochemistry 2017, 56: 2096-2105. PMID: 28326765, PMCID: PMC5522186, DOI: 10.1021/acs.biochem.6b01230.Peer-Reviewed Original ResearchDNA Polymerase Beta Germline Variant Confers Cellular Response to Cisplatin Therapy
Nemec AA, Abriola L, Merkel JS, de Stanchina E, DeVeaux M, Zelterman D, Glazer PM, Sweasy JB. DNA Polymerase Beta Germline Variant Confers Cellular Response to Cisplatin Therapy. Molecular Cancer Research 2017, 15: 269-280. PMID: 28074003, PMCID: PMC5334281, DOI: 10.1158/1541-7786.mcr-16-0227-t.Peer-Reviewed Original ResearchConceptsPrognostic biomarker potentialMouse xenograft modelLung cancer cellsPoor prognosisTreatment of cancerLung cancerSpecific chemotherapyXenograft modelPromising biomarkerMouse xenograftsMutational statusCancer ResChemotherapyGermline mutationsNucleotide excision repair pathwayBiomarker potentialCancer chemotherapyCancer treatmentCarrier statusCisplatinCancer cellsTumorsCancerTreatmentCell death
2014
Mutation of POLB Causes Lupus in Mice
Senejani AG, Liu Y, Kidane D, Maher SE, Zeiss CJ, Park HJ, Kashgarian M, McNiff JM, Zelterman D, Bothwell AL, Sweasy JB. Mutation of POLB Causes Lupus in Mice. Cell Reports 2014, 6: 1-8. PMID: 24388753, PMCID: PMC3916967, DOI: 10.1016/j.celrep.2013.12.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA Polymerase betaLupus Erythematosus, SystemicMiceMice, Inbred C57BLMutation, MissensePolymorphism, Single NucleotideV(D)J RecombinationConceptsSystemic lupus erythematosusLupus-like diseaseLupus erythematosusAutoimmune pathologyMouse modelGenome-wide association studiesPol β activityDecreased expressionMutant miceUnderlying causeMicePrevious genome-wide association studyΒ activityDNA polymerase activityReplication studyExcision repair pathwayImmune diversitySomatic hypermutationBase excision repair pathwayAssociation studiesErythematosusLupusPolymerase activityExpressionKey enzyme
2012
Y265C DNA polymerase beta knockin mice survive past birth and accumulate base excision repair intermediate substrates
Senejani AG, Dalal S, Liu Y, Nottoli TP, McGrath JM, Clairmont CS, Sweasy JB. Y265C DNA polymerase beta knockin mice survive past birth and accumulate base excision repair intermediate substrates. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 6632-6637. PMID: 22493258, PMCID: PMC3340078, DOI: 10.1073/pnas.1200800109.Peer-Reviewed Original ResearchConceptsDNA polymerase activityWT littermatesKnockin miceMiceMouse embryo fibroblastsChromosomal aberrationsWT mouse embryo fibroblastsNormal Mendelian ratioSlow proliferationPolymerase activityBirthΒ variantCell deathEmbryo fibroblastsWT cellsExcision repair pathwayDNA repair systemsCellular metabolismBase excision repair pathwayFibroblastsHoursHigh levelsHomozygous mutantsKey players
2004
Is there a link between DNA polymerase beta and cancer?
Starcevic D, Dalal S, Sweasy J. Is there a link between DNA polymerase beta and cancer? Cell Cycle 2004, 3: 998-1001. PMID: 15280658.Peer-Reviewed Original Research