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
A mitosis-specific and R loop–driven ATR pathway promotes faithful chromosome segregation
Kabeche L, Nguyen HD, Buisson R, Zou L. A mitosis-specific and R loop–driven ATR pathway promotes faithful chromosome segregation. Science 2017, 359: 108-114. PMID: 29170278, PMCID: PMC5875943, DOI: 10.1126/science.aan6490.Peer-Reviewed Original ResearchConceptsFaithful chromosome segregationChromosome segregationR-loopsATR pathwayCyclin-dependent kinase 1 (CDK1) activityWhole chromosome missegregationReplication stress responseReplication protein ADNA damage responseCentromere protein FKinase 1 activityATR functionAurora BDamage responseChromosome instabilityCentromeresProtein FAtaxia telangiectasiaAurora AUnexpected roleStress responseDNA damageDNA synthesisATRProtein AA bifurcated signaling cascade of NIMA-related kinases controls distinct kinesins in anaphase
Cullati SN, Kabeche L, Kettenbach AN, Gerber SA. A bifurcated signaling cascade of NIMA-related kinases controls distinct kinesins in anaphase. Journal Of Cell Biology 2017, 216: 2339-2354. PMID: 28630147, PMCID: PMC5551695, DOI: 10.1083/jcb.201512055.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnaphaseChromatography, AffinityCytokinesisHeLa CellsHumansHydrolysisIntracellular Signaling Peptides and ProteinsKinesinsNIMA-Related KinasesOncogene ProteinsPhosphorylationProtein Serine-Threonine KinasesRNA InterferenceSignal TransductionSpindle ApparatusTandem Mass SpectrometryTime FactorsTransfectionConceptsProtein-protein interactionsAnaphase central spindleNEK kinasesKinase NEK6Distinct kinesinsBundling activityPosttranslational modificationsCentral spindleCytoskeletal structuresNek9MKlp2Genetic materialTimely localizationKinesinCytokinesisNEK6Sophisticated networkKinaseNIMANEK7KIF14CascadeAnaphaseLocalizationMidzoneMitotic 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
Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation
Meppelink A, Kabeche L, Vromans MJ, Compton DA, Lens SM. Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation. Cell Reports 2015, 11: 508-515. PMID: 25892238, PMCID: PMC4718550, DOI: 10.1016/j.celrep.2015.03.052.Peer-Reviewed Original ResearchNumerical 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
Regulation of kinetochore–microtubule attachments through homeostatic control during mitosis
Godek KM, Kabeche L, Compton DA. Regulation of kinetochore–microtubule attachments through homeostatic control during mitosis. Nature Reviews Molecular Cell Biology 2014, 16: 57-64. PMID: 25466864, PMCID: PMC4568440, DOI: 10.1038/nrm3916.Peer-Reviewed Original ResearchDNA-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 cellsSTAG2 promotes error correction in mitosis by regulating kinetochore–microtubule attachments
Kleyman M, Kabeche L, Compton DA. STAG2 promotes error correction in mitosis by regulating kinetochore–microtubule attachments. Journal Of Cell Science 2014, 127: 4225-4233. PMID: 25074805, PMCID: PMC4179491, DOI: 10.1242/jcs.151613.Peer-Reviewed Original Research
2013
Cyclin A regulates kinetochore microtubules to promote faithful chromosome segregation
Kabeche L, Compton DA. Cyclin A regulates kinetochore microtubules to promote faithful chromosome segregation. Nature 2013, 502: 110-113. PMID: 24013174, PMCID: PMC3791168, DOI: 10.1038/nature12507.Peer-Reviewed Original Research
2012
Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments
Maia AR, Garcia Z, Kabeche L, Barisic M, Maffini S, Macedo-Ribeiro S, Cheeseman IM, Compton DA, Kaverina I, Maiato H. Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments. Journal Of Cell Biology 2012, 199: 285-301. PMID: 23045552, PMCID: PMC3471233, DOI: 10.1083/jcb.201203091.Peer-Reviewed Original ResearchConceptsSpindle assembly checkpointKT-MT attachmentsChromosome alignmentAccurate chromosome segregationC-terminal phosphorylationKinetochore-microtubule attachmentsUnderlying regulatory mechanismsPlk1 recruitmentMitosis reliesChromosome segregationChromosome movementMT attachmentPlk1 kinaseSpindle bipolarityMicrotubule interfaceMT dynamicsRegulatory mechanismsCLASP2Plk1CDK1PhosphorylationAttachment stabilityKinetochoresMitosisKinase