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 A
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
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
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