2024
A TRilogy of ATR’s Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer
Joo Y, Ramirez C, Kabeche L. A TRilogy of ATR’s Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer. Cancers 2024, 16: 3536. PMID: 39456630, PMCID: PMC11506335, DOI: 10.3390/cancers16203536.Peer-Reviewed Original ResearchDNA damage responseNon-canonical rolesCell cyclePromote faithful chromosome segregationDetect mechanical forcesDNA damage response pathwayFaithful chromosome segregationDNA damage checkpointRad3-related proteinNuclear membrane integrityCancer therapy targetATR inhibitorsChromosome segregationDamage checkpointDamage responseApical kinaseDamaged DNAMembrane integrityAtaxia telangiectasiaNon-canonicalCancer cellsDNAClinical trialsCancer therapyClinical relevance
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 populationsCGASCellsMicronucleiRad3GenomeChromothripsis
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
2014
DNA-Damage Response during Mitosis Induces Whole-Chromosome Missegregation
Bakhoum SF, Kabeche L, Murnane JP, Zaki BI, Compton DA. DNA-Damage Response during Mitosis Induces Whole-Chromosome Missegregation. Cancer Discovery 2014, 4: 1281-1289. PMID: 25107667, PMCID: PMC4221427, DOI: 10.1158/2159-8290.cd-14-0403.Peer-Reviewed Original ResearchConceptsDNA damage responseNumerical chromosomal instabilityDNA damageChromosome segregationChromosomal instabilityWhole chromosomal instabilityChromosome segregation defectsDefective chromosome segregationWhole chromosome missegregationChromosome segregation errorsPersistent DNA damageS-CINW-CINSegregation defectsMicrotubule attachmentDDR proteinsEntire chromosomesPlk1 kinaseCell divisionSegregation errorsMitotic processesChromosomesMitosisStructural rearrangementsCancer cells