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 ResearchConceptsSinglet molecular oxygenOxidation of serotoninMolecular oxygenElectron excitationTriplet stateAdjacent pyrimidine basesAbsence of lightEnergy transferDark processPyrimidine basesSkin pigment melaninBiochemical reactionsMoleculesEnergy levelsCatecholamine neurotransmittersBiomoleculesCycloadditionUltravioletMammalian metabolismCyclobutane pyrimidine dimersOxidationAminesPigment melaninRadicalsPeroxynitrite
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 ResearchConceptsCyclobutane 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
Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends
Chaudhuri RK, Meyer T, Premi S, Brash D. Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends. International Journal Of Cosmetic Science 2019, 42: 36-45. PMID: 31538664, PMCID: PMC7004018, DOI: 10.1111/ics.12582.Peer-Reviewed Original ResearchConceptsSun exposureSolar-simulated ultraviolet radiationReactive oxygen speciesIntracellular levelsCyclobutane pyrimidine dimersΑ-tocopherolCPD formationTraditional sunscreensScavenge peroxynitriteUVR exposureOngoing DNA damageAntioxidant α-tocopherolUltraviolet radiationUVA radiationMelanocytesROS formationExposureQuench singlet oxygenUse of AZEfficacyOxygen speciesKeratinocytesDNA damageFree radicalsHoursGenomic 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 sites
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
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
Influence 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
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 cells
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 radiation
2003
Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice
Wikonkal NM, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, Berton TR, Johnson DG, Brash DE. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nature Cell Biology 2003, 5: 655-660. PMID: 12833065, DOI: 10.1038/ncb1001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Cycle ProteinsCell SurvivalCell Transformation, NeoplasticCells, CulturedDNA DamageDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorFemaleFibroblastsGene Expression Regulation, NeoplasticGenes, SuppressorKeratinocytesMaleMiceMice, KnockoutMutationSex RatioSkin NeoplasmsTranscription FactorsTumor Suppressor Protein p53Ultraviolet RaysConceptsUVB-induced apoptosisEarly-onset tumorsDouble knockout miceTrp53-deficient miceKnockout miceCancer sensitivityUVB exposureGenetic abnormalitiesMiceKeratinocyte apoptosisProtective mechanismApoptosis defectsApoptosis resistanceApoptosisDouble knockoutApoptosis pathwayE2F1 transcription factorE2F1 functionsPrimary fibroblastsE2F1Trp53S phase
2001
The DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes
Brash D, Wikonkal N, Remenyik E, van der Horst G, Friedberg E, Cheo D, van Steeg H, Westerman A, van Kranen H. The DNA Damage Signal for Mdm2 Regulation, Trp53 Induction, and Sunburn Cell Formation In Vivo Originates from Actively Transcribed Genes. Journal Of Investigative Dermatology 2001, 117: 1234-1240. PMID: 11710938, DOI: 10.1046/j.0022-202x.2001.01554.x.Peer-Reviewed Original ResearchConceptsDNA photoproductsDNA damage signalsUnrepaired DNA lesionsCell formationSpecific genome regionsTumor suppressor proteinCsb-/- miceUltraviolet-induced apoptosisNucleotide excision repair genesApoptosis signal pathwayExcision repair genesActive genesMutant cellsGenome regionsDNA repairSuppressor proteinDamage signalsMDM2 regulationWild typeDNA lesionsPrevents cellsHomozygous inactivationGenesRepair genesDNA signals
1996
Sunlight and skin cancer.
Leffell DJ, Brash DE. Sunlight and skin cancer. Scientific American 1996, 275: 52-3, 56-9. PMID: 8658110, DOI: 10.1038/scientificamerican0796-52.Publications for non-academic audiencesTumor Suppressor Gene Mutations and Photocarcinogenesis
Ziegler A, Jonason A, Simon J, Leffell D, Brash DE. Tumor Suppressor Gene Mutations and Photocarcinogenesis. Photochemistry And Photobiology 1996, 63: 432-435. PMID: 8934758, DOI: 10.1111/j.1751-1097.1996.tb03064.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1990
Defective DNA Repair in Humans: Clinical and Molecular Studies of Xeroderma Pigmentosum
Kraemer K, Seetharam S, Seidman M, Bredberg A, Brash D, Waters H, Protić-Sablijć M, Peck G, DiGiovanna J, Moshell A, Tarone R, Jones G, Parshad R, Sanford K. Defective DNA Repair in Humans: Clinical and Molecular Studies of Xeroderma Pigmentosum. Basic Life Sciences 1990, 53: 95-104. PMID: 2282051, DOI: 10.1007/978-1-4613-0637-5_7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements