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 populationsCGASCellsMicronucleiRad3GenomeChromothripsisATR protects centromere identity by promoting DAXX association with PML nuclear bodies
Trier I, Black E, Joo Y, Kabeche L. ATR protects centromere identity by promoting DAXX association with PML nuclear bodies. Cell Reports 2023, 42: 112495. PMID: 37163376, DOI: 10.1016/j.celrep.2023.112495.Peer-Reviewed Original ResearchConceptsCentromere identityInterphase centromeresNuclear bodiesDNA damage-independent mannerPromyelocytic leukemia nuclear bodiesMitotic chromosome segregationCentromere protein AATR inhibitionDNA damage responsePML nuclear bodiesATR-dependent phosphorylationAcute ATR inhibitionChaperone DAXXGenome stabilityChromosome segregationPML-NBsDamage responseUnperturbed cellsMaster regulatorAtaxia telangiectasiaC-terminusFormation defectsCentromeresCENPAberrant increase
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