2025
Protein–Protein Interactions in Base Excision Repair
Rathnaiah G, Sweasy J. Protein–Protein Interactions in Base Excision Repair. Biomolecules 2025, 15: 890. PMID: 40563529, PMCID: PMC12190888, DOI: 10.3390/biom15060890.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsBase excision repairPolynucleotide kinase-phosphataseApurinic/apyrimidinic endonuclease 1X-ray repair cross-complementing protein 1Single-nucleotide base excision repairBase excision repair componentsExcision repairDNA polymerase BBase excision repair pathwayRepair of damaged basesDNA repair processesCore enzymePolymerase BDNA intermediatesProtein-proteinDamaged basesSingle-nucleotideDNA glycosylaseMolecular networksMolecular underpinningsDNAFunctional evidenceProtein 1EnzymeTranscription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination
Wu L, Yadavalli A, Senigl F, Matos-Rodrigues G, Xu D, Pintado-Urbanc A, Simon M, Wu W, Nussenzweig A, Schatz D. Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination. Molecular Cell 2025, 85: 1296-1310.e7. PMID: 40049160, PMCID: PMC11972161, DOI: 10.1016/j.molcel.2025.02.007.Peer-Reviewed Original ResearchRNA polymerase IITranscription-coupled nucleotide excision repairActivation-induced deaminaseClass switch recombinationSomatic hypermutationRNA polymerase II elongation complexDownstream of transcription start sitesRNA polymerase II transcriptionTranscription start siteSwitch recombinationMammalian B cellsImmunoglobulin (Ig) genesDNA cytidine deaminaseNucleotide excision repairPolymerase IISerine 5Transcribed genesTranscription elongationElongation complexStart siteGenetic screeningELOF1Excision repairTranscriptionProximity partners
2024
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, PMCID: PMC11611610, 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 mechanismsStrand-resolved mutagenicity of DNA damage and repair
Anderson C, Talmane L, Luft J, Connelly J, Nicholson M, Verburg J, Pich O, Campbell S, Giaisi M, Wei P, Sundaram V, Connor F, Ginno P, Sasaki T, Gilbert D, López-Bigas N, Semple C, Odom D, Aitken S, Taylor M. Strand-resolved mutagenicity of DNA damage and repair. Nature 2024, 630: 744-751. PMID: 38867042, PMCID: PMC11186772, DOI: 10.1038/s41586-024-07490-1.Peer-Reviewed Original ResearchConceptsDNA damageDNA damage-induced mutationsSingle-base resolutionCancer genome evolutionDamage-induced mutationsRepair of DNA damageNucleotide excision repairGenome evolutionMultiple distinct mutationsDNA accessibilityGenomic conditionsReplicative strandProcess genomesDNA base damageTranslesion polymerasesExcision repairDNAMutation patternsMutationsBase damageRepair efficiencyStrandsAlkyl adductsReplicationIdentity fidelityIntegrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix
Bellone S, Jeong K, Halle M, Krakstad C, McNamara B, Greenman M, Mutlu L, Demirkiran C, Hartwich T, Yang-Hartwich Y, Zipponi M, Buza N, Hui P, Raspagliesi F, Lopez S, Paolini B, Milione M, Perrone E, Scambia G, Altwerger G, Ravaggi A, Bignotti E, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Quick C, Angioli R, Terranova C, Zaidi S, Nandi S, Alexandrov L, Siegel E, Choi J, Schlessinger J, Santin A. Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321898121. PMID: 38625939, PMCID: PMC11046577, DOI: 10.1073/pnas.2321898121.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingPatient-derived-xenograftsBase excision repairCopy number lossMultiregion whole-exome sequencingCopy number gainHigh-grade neuroendocrine carcinomaCNV analysisPhylogenetic analysisEvolutionary historyNeuroendocrine cervical cancerHuman papillomavirus DNAMutator phenotypeSensitivity to afatinibGenetic landscapeRecurrent mutationsRNA sequencingGene fusionsMutational landscape analysisExcision repairGenesMutationsPan-HERConsistent with deficiencyNeuroendocrine carcinoma
2022
Proteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells
Wang Y, Chen Y, Garcia-Milian R, Golla JP, Charkoftaki G, Lam TT, Thompson DC, Vasiliou V. Proteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells. Chemico-Biological Interactions 2022, 368: 110175. PMID: 36162455, PMCID: PMC9891852, DOI: 10.1016/j.cbi.2022.110175.Peer-Reviewed Original ResearchConceptsCancer stem cellsProteomic profilingOxidative phosphorylationLabel-free quantitative proteomic analysisDNA damage repair pathwaysQuantitative proteomic analysisAldehyde dehydrogenase familyColon cancer stem cellsCOLO320DM cellsStem cellsNucleotide excision repairDamage repair pathwaysIngenuity Pathway AnalysisCell populationsProteomic analysisProteomic datasetsDehydrogenase familyMetabolic switchProteomic studiesRepair pathwaysCellular pathwaysALDH enzymatic activityCellular survivalExcision repairALDH activityAn ELISA-based platform for rapid identification of structure-dependent nucleic acid–protein interactions detects novel DNA triplex interactors
Economos NG, Thapar U, Balasubramanian N, Karras GI, Glazer PM. An ELISA-based platform for rapid identification of structure-dependent nucleic acid–protein interactions detects novel DNA triplex interactors. Journal Of Biological Chemistry 2022, 298: 102398. PMID: 35988651, PMCID: PMC9493393, DOI: 10.1016/j.jbc.2022.102398.Peer-Reviewed Original ResearchConceptsNucleic acid structuresNucleic acid-protein interactionsNucleotide excision repairSingle-strand annealing repairDouble-strand break intermediatesUnusual nucleic acid structuresNovel interactorNucleic acid interactionsHigh-throughput platformCellular processesFactor localizationAcid structureExcision repairRelevant lociHuman cellsGene editingAcid interactionsInteractorsTherapeutic gene editingNucleic acidsDNA triplexesRapid identificationComparative approachGenomeTriplexes
2020
EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair
Koyen A, Madden M, Park D, Minten E, Kapoor-Vazirani P, Werner E, Pfister N, Haji-Seyed-Javadi R, Zhang H, Xu J, Deng N, Duong D, Pecen T, Frazier Z, Nagel Z, Lazaro J, Mouw K, Seyfried N, Moreno C, Owonikoko T, Deng X, Yu D. EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair. Oncogene 2020, 39: 4798-4813. PMID: 32457468, PMCID: PMC7305988, DOI: 10.1038/s41388-020-1332-2.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerCisplatin resistanceSCLC cellsCisplatin-based chemotherapyCell lung cancerImportant therapeutic targetZeste homolog 2Cellular cisplatinPoor outcomeAggressive malignancyNucleotide excision repairLung cancerClinical investigationTherapeutic targetEZH2 depletionPolycomb repressive complex 2Homolog 2DDB1-DDB2EZH2Important regulatorRepairExcision repairMethyltransferase activityPRC2-independent functionSynthetic lethality screen
2019
Impact of hypoxia on DNA repair and genome integrity
Kaplan AR, Glazer PM. Impact of hypoxia on DNA repair and genome integrity. Mutagenesis 2019, 35: 61-68. PMID: 31282537, PMCID: PMC7317153, DOI: 10.1093/mutage/gez019.Peer-Reviewed Original ResearchConceptsDNA repairDNA repair pathwaysHomology-directed repairBase excision repairGenome integrityRepair pathwaysGenomic instabilityExcision repairHypoxia mimeticMismatch repairDiverse mechanismsImpact of hypoxiaCancer progressionMutation frequencyTumor biologyTumor microenvironmentDevelopment of metastasesPotential clinical relevanceProfound effectRepairBiologyHypoxiaPathwayHallmarkMicroenvironment
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 Specificity
2015
Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment
Scanlon SE, Glazer PM. Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment. DNA Repair 2015, 32: 180-189. PMID: 25956861, PMCID: PMC4522377, DOI: 10.1016/j.dnarep.2015.04.030.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA repair pathwaysRepair pathwaysDNA repairCertain DNA repair genesMost DNA repair pathwaysDNA double-strand break repairDouble-strand break repairPost-translational modificationsNucleotide excision repairDNA repair genesTumor suppressor geneMultifaceted controlTranslational downregulationEpigenetic levelBreak repairMutator phenotypeCellular consequencesGenomic instabilityExcision repairHypoxic cancer cellsSuppressor geneIntra-tumor heterogeneityMismatch repairPersistent silencingDNA damage
2013
Early days of DNA repair: discovery of nucleotide excision repair and homology-dependent recombinational repair.
Rupp WD. Early days of DNA repair: discovery of nucleotide excision repair and homology-dependent recombinational repair. The Yale Journal Of Biology And Medicine 2013, 86: 499-505. PMID: 24348214, PMCID: PMC3848104.Peer-Reviewed Original ResearchConceptsHomology-dependent recombinational repairNucleotide excision repairRepairExcision repairFurther researchHypoxia and DNA repair.
Glazer PM, Hegan DC, Lu Y, Czochor J, Scanlon SE. Hypoxia and DNA repair. The Yale Journal Of Biology And Medicine 2013, 86: 443-51. PMID: 24348208, PMCID: PMC3848098.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA repairHomology-dependent repairDNA repair pathwaysNucleotide excision repairDNA mismatch repairGenomic integrityDependent repairCell physiologyRepair pathwaysExcision repairHypoxic cancer cellsCell metabolismGenetic instabilityMismatch repairInduction of angiogenesisCancer progressionCell growthCancer cellsNeoplastic developmentRepairSolid tumorsKey componentHypoxiaProfound changesApoptosisGenetic Instability Induced by Hypoxic Stress
Scanlon S, Glazer P. Genetic Instability Induced by Hypoxic Stress. 2013, 151-181. DOI: 10.1007/978-1-4614-6280-4_8.ChaptersGenetic instabilityCell cycle checkpointsDNA repair pathwaysNucleotide excision repairHypoxic stress responseHomologous recombination repairGenomic integrityCellular machineryCycle checkpointsRepair pathwaysGenomic instabilityExcision repairRecombination repairStress responseApoptotic pathwayGenetic evolutionCellular responsesMismatch repairSignificant physiological stressCancer biologyDNA damageCancer progressionCell growthDNA damage rateHypoxic stress
2012
Rules of engagement for base excision repair in chromatin
Odell ID, Wallace SS, Pederson DS. Rules of engagement for base excision repair in chromatin. Journal Of Cellular Physiology 2012, 228: 258-266. PMID: 22718094, PMCID: PMC3468691, DOI: 10.1002/jcp.24134.Peer-Reviewed Original ResearchConceptsBase excision repairSingle-strand break repairNucleotide excision repairHomology-directed repairExcision repairCheckpoint activationCell cycle checkpoint activationStrand break repair pathwaysDouble-strand break repair pathwayStrand break repairBreak repair pathwayOxidative damage resultsNucleosome disruptionDNA replicationBreak repairRepair pathwaysDNA segmentsChromatinEfficient repairNumerous DNAOxidative DNA damageRegulatory factorsHuman cellsNucleosomesDNA damageHuman POLB Gene Is Mutated in High Percentage of Colorectal Tumors*
Donigan KA, Sun KW, Nemec AA, Murphy DL, Cong X, Northrup V, Zelterman D, Sweasy JB. Human POLB Gene Is Mutated in High Percentage of Colorectal Tumors*. Journal Of Biological Chemistry 2012, 287: 23830-23839. PMID: 22577134, PMCID: PMC3390656, DOI: 10.1074/jbc.m111.324947.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBinding SitesBiocatalysisCell SurvivalCells, CulturedColorectal NeoplasmsDNA Polymerase betaEmbryo, MammalianFibroblastsGenetic Complementation TestHEK293 CellsHumansKineticsMethyl MethanesulfonateMiceMice, KnockoutModels, MolecularMutagensMutationMutation RateNeoplasm StagingProtein Structure, TertiaryConceptsPolB geneGenomic instabilityEnzyme functionBase excision repair functionNonsynonymous amino acid substitutionsExcision repair functionBase excision repairEnzyme activityAmino acid substitutionsCellular transformationExcision repairRepair functionDeficient cellsSequencing studiesAcid substitutionsPol βΒ variantΒ-proteinTissue originHuman colorectal tumorsGenesRegion mutationsHuman tumorsTumorigenesisVariants
2011
Nucleosome Disruption by DNA Ligase III-XRCC1 Promotes Efficient Base Excision Repair
Odell ID, Barbour JE, Murphy DL, Della-Maria JA, Sweasy JB, Tomkinson AE, Wallace SS, Pederson DS. Nucleosome Disruption by DNA Ligase III-XRCC1 Promotes Efficient Base Excision Repair. Molecular And Cellular Biology 2011, 31: 4623-4632. PMID: 21930793, PMCID: PMC3209256, DOI: 10.1128/mcb.05715-11.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDeoxyribonuclease (Pyrimidine Dimer)DNADNA DamageDNA GlycosylasesDNA Ligase ATPDNA LigasesDNA Polymerase betaDNA RepairDNA-(Apurinic or Apyrimidinic Site) LyaseDNA-Binding ProteinsHumansLytechinusNucleosomesPoly-ADP-Ribose Binding ProteinsReactive Oxygen SpeciesX-ray Repair Cross Complementing Protein 1XenopusXenopus ProteinsConceptsBase excision repairNucleosome disruptionApurinic endonucleaseExcision repairEfficient base excision repairNucleated human cellsDNA polymerase βNucleosome substratesRibosomal DNASingle base gapHuman cellsNucleosomesDNA ligasePolymerase βPol βRate-limiting stepHNTH1Ternary complexDNAUnique roleChromatinLigaseDisruptionEndonucleaseLesions formPolymorphism in the DNA repair enzyme XRCC1: Utility of current database and implications for human health risk assessment
Ginsberg G, Angle K, Guyton K, Sonawane B. Polymorphism in the DNA repair enzyme XRCC1: Utility of current database and implications for human health risk assessment. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 2011, 727: 1-15. PMID: 21352951, DOI: 10.1016/j.mrrev.2011.02.001.Peer-Reviewed Original ResearchConceptsBase excision repairDNA repairGene expressionRepair functionUpstream regulatory sequencesDNA damaging agentsHomozygous variantToxicodynamic responseXRCC1 levelsRegulatory sequencesBinding sequenceExcision repairDamaging agentsProtein structureBER genesDNA damageAllele frequenciesCurrent databasePolymorphismGenotype effectsArg399Gln variantPhenotypeGenetic polymorphismsXRCC1Environmental agents
2010
Variation Within DNA Repair Pathway Genes and Risk of Multiple Sclerosis
Briggs FB, Goldstein BA, McCauley JL, Zuvich RL, De Jager PL, Rioux JD, Ivinson AJ, Compston A, Hafler DA, Hauser SL, Oksenberg JR, Sawcer SJ, Pericak-Vance MA, Haines JL, Barcellos LF, Consortium F. Variation Within DNA Repair Pathway Genes and Risk of Multiple Sclerosis. American Journal Of Epidemiology 2010, 172: 217-224. PMID: 20522537, PMCID: PMC3658128, DOI: 10.1093/aje/kwq086.Peer-Reviewed Original ResearchConceptsDNA repair pathway genesPathway genesMultiple sclerosisExcision repairGeneral transcription factor IIHDouble-strand break repairTranscription factor IIHDNA repair pathwaysNucleotide excision repairRisk of MSBase excision repairPrimary genetic risk factorProminent genetic componentHuman leukocyte antigenComplex autoimmune diseaseSingle nucleotide polymorphism (SNP) variantsCentral nervous systemLogistic regression modelingGenetic risk factorsSingle nucleotide polymorphismsBreak repairRepair pathwaysCandidate genesAutoimmune diseasesGenes
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply