2023
Chemiexcited Neurotransmitters and Hormones Create DNA Photoproducts in the Dark
Gonçalves L, Angelé-Martínez C, Premi S, Palmatier M, Prado F, Di Mascio P, Bastos E, Brash D. Chemiexcited Neurotransmitters and Hormones Create DNA Photoproducts in the Dark. ACS Chemical Biology 2023, 18: 484-493. PMID: 36775999, PMCID: PMC10276651, DOI: 10.1021/acschembio.2c00787.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNADNA DamageHormonesMammalsMelaninsNeurotransmitter AgentsPeroxynitrous AcidPyrimidine DimersUltraviolet RaysConceptsSinglet molecular oxygenOxidation of serotoninMolecular oxygenElectron excitationTriplet stateAdjacent pyrimidine basesAbsence of lightEnergy transferDark processPyrimidine basesSkin pigment melaninBiochemical reactionsMoleculesEnergy levelsCatecholamine neurotransmittersBiomoleculesCycloadditionUltravioletMammalian metabolismCyclobutane pyrimidine dimersOxidationAminesPigment melaninRadicalsPeroxynitriteChemiexcitation: Mammalian Photochemistry in the Dark†
Brash D, Goncalves L. Chemiexcitation: Mammalian Photochemistry in the Dark†. Photochemistry And Photobiology 2023, 99: 251-276. PMID: 36681894, PMCID: PMC10065968, DOI: 10.1111/php.13781.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsExcited statesMammalian cellsCyclobutane pyrimidine dimersEvolutionary selectionBond rearrangementUnoccupied orbitalsGround stateReaction productsPyrimidine dimersChemiexcitationRecent findingsBiologyPathogenic eventsRadicalsUltraviolet lightMoleculesDrug-induced deafnessPotential pathogenesisCellsMelaninAchilles heelMammalsBiomoleculesPhotochemistryDNA
2022
Cyclobutane Pyrimidine Dimer Hyperhotspots as Sensitive Indicators of Keratinocyte UV Exposure†
Garcia‐Ruiz A, Kornacker K, Brash DE. Cyclobutane Pyrimidine Dimer Hyperhotspots as Sensitive Indicators of Keratinocyte UV Exposure†. Photochemistry And Photobiology 2022, 98: 987-997. PMID: 35944237, PMCID: PMC9802031, DOI: 10.1111/php.13683.Peer-Reviewed Original ResearchMeSH KeywordsDNA DamageHumansInfant, NewbornKeratinocytesPyrimidine DimersReproducibility of ResultsTranscription FactorsUltraviolet RaysConceptsCyclobutane pyrimidine dimersGenomic averageSequence motifsHigh-throughput DNA sequencing methodsETS family transcription factorsNucleotide resolution analysisRNA processing genesNeonatal human epidermal keratinocytesDNA sequencing methodsTranscription factorsCpG islandsSites hundredsCell physiologyProcessing genesPromoter regionCell deathDNA damageSequencing methodsBiological importanceHuman epidermal keratinocytesPyrimidine dimersGenesMotifEpidermal keratinocytesMelanocytes
2019
Defective postreplication repair of UV photoproducts in melanoma: a mutator phenotype
Brash DE, Seidman MM. Defective postreplication repair of UV photoproducts in melanoma: a mutator phenotype. Molecular Oncology 2019, 14: 5-7. PMID: 31821728, PMCID: PMC6944110, DOI: 10.1002/1878-0261.12612.Commentaries, Editorials and LettersGenomic sites hypersensitive to ultraviolet radiation
Premi S, Han L, Mehta S, Knight J, Zhao D, Palmatier MA, Kornacker K, Brash DE. Genomic sites hypersensitive to ultraviolet radiation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24196-24205. PMID: 31723047, PMCID: PMC6883822, DOI: 10.1073/pnas.1907860116.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsCells, CulturedDNA DamageFibroblastsGene Expression RegulationGenome, HumanHigh-Throughput Nucleotide SequencingHumansMelanocytesMelanomaMutationPromoter Regions, GeneticProtein BiosynthesisPyrimidine DimersPyrimidine NucleotidesSkin NeoplasmsTOR Serine-Threonine KinasesUltraviolet RaysConceptsCyclobutane pyrimidine dimersETS family transcription factorsIndividual gene promotersFamily transcription factorsRNA-binding proteinPrimary human melanocytesSingle-base resolutionEpigenetic marksGenomic averageTranslation regulationGenomic sitesMotif locationsTranscription factorsCell physiologyGene promoterCancer driversGenomeHuman melanocytesCell typesTumor evolutionCell pathwaysRare mutationsUV targetPyrimidine dimersApurinic sitesAccelerating cancer without mutations
Brash DE. Accelerating cancer without mutations. ELife 2019, 8: e45809. PMID: 30895924, PMCID: PMC6428566, DOI: 10.7554/elife.45809.Commentaries, Editorials and Letters
2016
Chemical excitation of electrons: A dark path to melanoma
Premi S, Brash DE. Chemical excitation of electrons: A dark path to melanoma. DNA Repair 2016, 44: 169-177. PMID: 27262612, PMCID: PMC4958542, DOI: 10.1016/j.dnarep.2016.05.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2015
Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure
Premi S, Wallisch S, Mano CM, Weiner AB, Bacchiocchi A, Wakamatsu K, Bechara EJ, Halaban R, Douki T, Brash DE. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 2015, 347: 842-847. PMID: 25700512, PMCID: PMC4432913, DOI: 10.1126/science.1256022.Peer-Reviewed Original ResearchConceptsDark cyclobutane pyrimidine dimersExcited electronic statesUltraviolet photonsUV photonsElectronic statesTriplet stateSunlight-induced melanomaCytosine-containing cyclobutane pyrimidine dimersEnergy transferPhotonsPicosecondsElectronsUV exposureRadiationChemiexcitationEnergyStatePhotoproducts
2014
UV Signature Mutations
Brash DE. UV Signature Mutations. Photochemistry And Photobiology 2014, 91: 15-26. PMID: 25354245, PMCID: PMC4294947, DOI: 10.1111/php.12377.Peer-Reviewed Original Research
2010
Human Telomeres Are Hypersensitive to UV-Induced DNA Damage and Refractory to Repair
Rochette PJ, Brash DE. Human Telomeres Are Hypersensitive to UV-Induced DNA Damage and Refractory to Repair. PLOS Genetics 2010, 6: e1000926. PMID: 20442874, PMCID: PMC2861706, DOI: 10.1371/journal.pgen.1000926.Peer-Reviewed Original ResearchConceptsUV-induced DNA damageDNA damageTelomeric repeatsHuman telomeresExcision repairTelomeric repeat unitsNucleotide excision repairDouble-strand breaksUV-induced CPDGenome integrityGenomic integrityExcision repair sitesMitochondrial DNARegion of p53Opposite strandTelomeresCPD removalUnrepaired lesionsRepeatsPreeminent risk factorUV sensitivityPyrimidine dimersCancer developmentRepeat unitsCritical role
2009
Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia
Klein AM, Brash DE, Jones PH, Simons BD. Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 107: 270-275. PMID: 20018764, PMCID: PMC2806764, DOI: 10.1073/pnas.0909738107.Peer-Reviewed Original ResearchConceptsP53 mutationsNonmelanoma skin cancer incidenceSame cumulative doseSkin cancer incidenceUVB radiationUV-irradiated epidermisP53 tumor suppressor geneP53-mutant clonesCumulative doseCancer incidenceP53 mutant cellsHigh-intensity exposureMurine epidermisPreneoplastic clonesTumor suppressor geneProgenitor cellsExposure resultsPrecancerous cellsPreneoplastic cellsHuman epidermisB radiationClones of cellsInfluence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA
Rochette PJ, Lacoste S, Therrien JP, Bastien N, Brash DE, Drouin R. Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 2009, 665: 7-13. PMID: 19427505, DOI: 10.1016/j.mrfmmm.2009.02.008.Peer-Reviewed Original ResearchConceptsLigation-mediated PCRX chromosomeFMR1 geneGenomic DNAInactive X chromosomeDimer formationCyclobutane pyrimidine dimer formationTumor suppressor genePyrimidine dimer formationConstitutive methylationCytosine methylationMethylated cytosineUnmethylated cytosinesSuppressor geneP53 tumor suppressor geneGenesMethylationCPD formationChromosomesCytosineDNAMutationsSunlight-induced mutationsDipyrimidine sitesPGK1
2008
Preneoplastic lesion growth driven by the death of adjacent normal stem cells
Chao DL, Eck JT, Brash DE, Maley CC, Luebeck EG. Preneoplastic lesion growth driven by the death of adjacent normal stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 15034-15039. PMID: 18815380, PMCID: PMC2567488, DOI: 10.1073/pnas.0802211105.Peer-Reviewed Original ResearchConceptsNormal stem cellsStem cellsClonal expansionCell replicationMutant cellsNormal cell replicationMutant clonesProliferative advantageDorsal epidermisCell mutationTissue architectureClonesClone growthBiological observationsCell killingApoptosis rateReplicationMutationsGrowth rateCellsGrowthNormal territoriesApoptosisExponential growth modelImportant step
2007
Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling
Knezevic D, Zhang W, Rochette PJ, Brash DE. Bcl-2 is the target of a UV-inducible apoptosis switch and a node for UV signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 11286-11291. PMID: 17586682, PMCID: PMC2040891, DOI: 10.1073/pnas.0701318104.Peer-Reviewed Original Research
2005
Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis
Chaturvedi V, Sitailo LA, Qin JZ, Bodner B, Denning MF, Curry J, Zhang W, Brash D, Nickoloff BJ. Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-xL reduction thereby enhancing UV-light induced apoptosis. Oncogene 2005, 24: 5299-5312. PMID: 15940268, DOI: 10.1038/sj.onc.1208650.Peer-Reviewed Original ResearchConceptsMouse modelP53 levelsP53 siRNAHuman keratinocytesMcl-1Skin cancer developmentKnockout mouse modelP53 tumor suppressor geneCultured human keratinocytesBcl-xL antiapoptotic proteinBcl-xL levelsCommon causeParadoxical responseSkin cancerAccelerated eliminationUltraviolet light exposureWild-type p53Cancer developmentTumor suppressor geneUV-induced DNA damageEpidermal responseE2F-1 levelsPrimary culturesSiRNA-based approachAbnormal cellsColonization of adjacent stem cell compartments by mutant keratinocytes
Brash DE, Zhang W, Grossman D, Takeuchi S. Colonization of adjacent stem cell compartments by mutant keratinocytes. Seminars In Cancer Biology 2005, 15: 97-102. PMID: 15652454, DOI: 10.1016/j.semcancer.2004.08.006.ChaptersMeSH KeywordsAnimalsApoptosisKeratinocytesMutagenesisSkin NeoplasmsStem CellsTumor Suppressor Protein p53Ultraviolet RaysConceptsStem cell compartmentMutant stem cellsCell compartmentStem cellsDNA-damaged cellsNon-mutational mechanismsMutant cellsAdditional genesClonal expansionSelection pressureP53 mutant cellsUVB-induced apoptosisMutant keratinocytesCancer developmentCompartmentsCellsAbsence of escapeKeratinocyte clonesAdditional territoryClinical phenotypeAdjacent compartmentsGenesMechanismClonesPhenotype
2004
Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin
Takeuchi S, Zhang W, Wakamatsu K, Ito S, Hearing VJ, Kraemer KH, Brash DE. Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 15076-15081. PMID: 15477596, PMCID: PMC524044, DOI: 10.1073/pnas.0403994101.Peer-Reviewed Original ResearchConceptsYellow miceTerminal deoxynucleotidyltransferase-mediated dUTP nickTUNEL-positive cellsActive caspase-3Sunburn cellsPositive cellsBlack miceSkin cancerCongenic miceMurine skinDUTP nickDNA strand breaksMiceEpidermal sheetsHair folliclesAbility of melaninCaspase-3Sensitivity of individualsApoptosisLesionsUVA radiationRed hairCell deathHair shaftSunlight UV radiationUVB-induced apoptosis drives clonal expansion during skin tumor development
Zhang W, Hanks AN, Boucher K, Florell SR, Allen SM, Alexander A, Brash DE, Grossman D. UVB-induced apoptosis drives clonal expansion during skin tumor development. Carcinogenesis 2004, 26: 249-257. PMID: 15498793, PMCID: PMC2292404, DOI: 10.1093/carcin/bgh300.Peer-Reviewed Original Research
2003
Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones
Remenyik É, Wikonkál NM, Zhang W, Paliwal V, Brash DE. Antigen-specific immunity does not mediate acute regression of UVB-induced p53-mutant clones. Oncogene 2003, 22: 6369-6376. PMID: 14508517, DOI: 10.1038/sj.onc.1206657.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHomeodomain ProteinsHumansImmune SystemMiceMice, KnockoutMutationTumor Suppressor Protein p53Ultraviolet RaysConceptsAntigen-specific immunityP53-mutant clonesUltraviolet BAcute regressionNatural killer T cellsKiller T cellsRag1 knockout miceChronic UVB irradiationMurine skin tumorsInduction of carcinomasSignificant differencesUVB carcinogenesisT cellsSkin tumorsKnockout micePersistence of clonesEpidermal thicknessMurine epidermisUVB irradiationEpidermal sheetsImmunityChronic irradiationGene 1MiceRegressionPhotocopying Cancer Cells
Brash DE. Photocopying Cancer Cells. Journal Of Investigative Dermatology 2003, 121: xiii-xiv. PMID: 12839596, DOI: 10.1046/j.1523-1747.2003.12381.x.Commentaries, Editorials and Letters