2023
ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei
Joo Y, Black E, Trier I, Haakma W, Zou L, Kabeche L. ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei. Molecular Cell 2023, 83: 3642-3658.e4. PMID: 37788673, PMCID: PMC10599252, DOI: 10.1016/j.molcel.2023.09.003.Peer-Reviewed Original ResearchConceptsATR inhibitorsLamin A/CCytoplasmic DNA sensor cGASHuman ataxia telangiectasiaDNA sensor cGASCdk1 phosphorylationGenomic integrityKinase functionMicronuclear DNAAtaxia telangiectasiaCDK1 inhibitionChromosomal instabilityS phaseAutonomous mechanismsAutophagosome accumulationATRCancer cellsDNACell populationsCGASCellsMicronucleiRad3GenomeChromothripsisMolecular mechanism of hyperactivation conferred by a truncation of TRPA1
Bali A, Schaefer S, Trier I, Zhang A, Kabeche L, Paulsen C. Molecular mechanism of hyperactivation conferred by a truncation of TRPA1. Nature Communications 2023, 14: 2867. PMID: 37208332, PMCID: PMC10199097, DOI: 10.1038/s41467-023-38542-1.Peer-Reviewed Original ResearchConceptsChannel sensitizationPlasma membraneHeterologous cellsGenetic analysisMolecular mechanismsBiochemical assaysHeteromeric channelsNonsense mutationPhysiological impactMutantsAgonist sensitivityCalcium permeabilityEnergetic barrierSubunitsTRPA1MutationsTractable mechanismMechanismHyperactivationMembraneCellsActivationAssaysGatingTruncation
2017
Mitotic DNA Damage Response: At the Crossroads of Structural and Numerical Cancer Chromosome Instabilities
Bakhoum SF, Kabeche L, Compton DA, Powell SN, Bastians H. Mitotic DNA Damage Response: At the Crossroads of Structural and Numerical Cancer Chromosome Instabilities. Trends In Cancer 2017, 3: 225-234. PMID: 28718433, PMCID: PMC5518619, DOI: 10.1016/j.trecan.2017.02.001.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDNA damage responseSegregation errorsMitotic DNA damage responseNovel anticancer therapeutic strategyMitotic DNA damageChromosome segregation errorsDouble-strand breaksNumerical chromosomal instabilityGenomic integrityDamage responseChromosome instabilityAnticancer therapeutic strategiesChromosomal instabilityGenomic damageDNA damageCancer cellsNormal cellsMitosisCellsUnstable tumorsActivation inducesTherapeutic strategiesPathwayThorough understanding
2016
Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition
Comaills V, Kabeche L, Morris R, Buisson R, Yu M, Madden MW, LiCausi JA, Boukhali M, Tajima K, Pan S, Aceto N, Sil S, Zheng Y, Sundaresan T, Yae T, Jordan NV, Miyamoto DT, Ting DT, Ramaswamy S, Haas W, Zou L, Haber DA, Maheswaran S. Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition. Cell Reports 2016, 17: 2632-2647. PMID: 27926867, PMCID: PMC5320932, DOI: 10.1016/j.celrep.2016.11.022.Peer-Reviewed Original ResearchConceptsGenomic instabilityCancer cellsNuclear envelope proteinsMesenchymal transitionHeritable genetic changesHeritable changesMitotic defectsMitotic regulationTumorigenic phenotypeProliferation arrestMicroenvironment-derived signalsMitotic abnormalitiesStromal signalsGenetic changesMesenchymal marker expressionCancer progressionReversible phenotypeEnvelope proteinEpithelial cellsPersistent proliferationPhenotypeCellsMarker expressionDrug resistanceTGF
2015
Numerical chromosomal instability mediates susceptibility to radiation treatment
Bakhoum SF, Kabeche L, Wood MD, Laucius CD, Qu D, Laughney AM, Reynolds GE, Louie RJ, Phillips J, Chan DA, Zaki BI, Murnane JP, Petritsch C, Compton DA. Numerical chromosomal instability mediates susceptibility to radiation treatment. Nature Communications 2015, 6: 5990. PMID: 25606712, PMCID: PMC4516720, DOI: 10.1038/ncomms6990.Peer-Reviewed Original ResearchConceptsWhole chromosome missegregationRadiation-induced genome damageChromosome missegregation ratesGenome damageChromosome segregation errorsNumerical chromosomal instabilityTumor-derived cell linesMitotic cancer cellsMitotic pathwaysSegregation errorsHuman glioblastoma tumorsMitotic cellsMitotic errorsChromosomal instabilityCell deathChromosomal breaksMissegregationCancer cellsCell linesGlioblastoma tumorsExquisite sensitivityIR leadCellsChromosomal defectsChromosomes