Global screening of base excision repair in nucleosome core particles
Sutton T, Sawyer D, Naila T, Sweasy J, Tomkinson A, Delaney S. Global screening of base excision repair in nucleosome core particles. DNA Repair 2024, 144: 103777. PMID: 39476546, DOI: 10.1016/j.dnarep.2024.103777.Peer-Reviewed Original ResearchBase excision repairUracil-DNA glycosylaseAP endonuclease 1Nucleosome core particleBase excision repair enzymesAbsence of chromatin remodelingExcision repairDNA polymerase BGenome wide mappingContext of chromatinEukaryotic genomic DNADNA damageCore particlesPolymerase BChromatin remodelingActivities of BER enzymesNick siteGenomic DNAProtein interactionsMutational hotspotsNucleosomal DNADNA glycosylaseGenomic instabilityCellular factorsEntry/exit regionCollapsed State Mediates the Low Fidelity of the DNA Polymerase β I260 Mutant
Fijen C, Chavira C, Alnajjar K, Sawyer D, Sweasy J. Collapsed State Mediates the Low Fidelity of the DNA Polymerase β I260 Mutant. Biochemistry 2024, 63: 2414-2424. PMID: 39299701, PMCID: PMC11448664, DOI: 10.1021/acs.biochem.4c00263.Peer-Reviewed Original ResearchPol-BI260MForster resonance energy transferNucleotide discriminationConformational changesDNA polymerase BTemperature-sensitive mutationAccurate DNA synthesisReduced fidelityBase excision repairContext-dependent mannerPolymerase BNoncovalent stepPolymerase fidelityBound nucleotideResonance energy transferIncreased mutagenesisGenomic instabilityFinger regionWT proteinExcision repairI260Rate of conformational changeTurnover kineticsMolecular mechanismsModifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β
Alnajjar K, Wang K, Alvarado-Cruz I, Chavira C, Negahbani A, Nakhjiri M, Minard C, Garcia-Barboza B, Kashemirov B, McKenna C, Goodman M, Sweasy J. Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β. Biochemistry 2024, 63: 1412-1422. PMID: 38780930, PMCID: PMC11155676, DOI: 10.1021/acs.biochem.4c00065.Peer-Reviewed Original ResearchDNA polymerase BPolymerase BPol-BBase excision DNA repair pathwayLinear free energy relationshipGapped DNA substratesRemoval of damaged DNA basesFree energy relationshipConformational changesChemical transition stateAccumulation of mutationsDNA repair pathwaysDamaged DNA basesGroup basicityCorrect nucleotideDNA substratesIncoming nucleotideTransition stateEnergy relationshipFingers subdomainRepair pathwaysSubstrate selectivityNucleotideTriphosphate moietyCatalytic function