2024
Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation
Black E, Ramírez Parrado C, Trier I, Li W, Joo Y, Pichurin J, Liu Y, Kabeche L. Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation. Nature Communications 2024, 15: 10782. PMID: 39737931, PMCID: PMC11685634, DOI: 10.1038/s41467-024-54922-7.Peer-Reviewed Original ResearchConceptsPolo-like kinase 1Plk1 activityChromosome segregationMitotic polo-like kinase 1Mitotic chromosome segregationProtecting genome stabilitySensitivity to PLK1 inhibitorsMitotic cell divisionCheckpoint kinase 2Polo-like kinase 1 activityDNA damage repairGenome stabilityChromosome missegregationCytokinetic defectsCell divisionGenomic instabilityT-loopCell cycleKinase activityChromosome misalignmentMitotic errorsChk2Kinase 2Damage repairChromosome
2021
Cell cycle regulation of ER membrane biogenesis protects against chromosome missegregation
Merta H, Carrasquillo Rodríguez JW, Anjur-Dietrich MI, Vitale T, Granade ME, Harris TE, Needleman DJ, Bahmanyar S. Cell cycle regulation of ER membrane biogenesis protects against chromosome missegregation. Developmental Cell 2021, 56: 3364-3379.e10. PMID: 34852214, PMCID: PMC8692360, DOI: 10.1016/j.devcel.2021.11.009.Peer-Reviewed Original ResearchConceptsChromosome missegregationEndoplasmic reticulumLipin-1Accurate chromosome segregationER membrane biogenesisCell cycle regulationPhosphatidic acid phosphatase lipin-1Chromosome segregationMembrane biogenesisER membraneChromosome movementMitotic fidelityCycle regulationER sizeMitosis resultsMitotic cytoplasmFormation of micronucleiMitotic cellsMitotic errorsMissegregationER reorganizationHuman cellsBiophysical propertiesCancer cellsLipid metabolismWhole-genome doubling confers unique genetic vulnerabilities on tumour cells
Quinton R, DiDomizio A, Vittoria M, Kotýnková K, Ticas C, Patel S, Koga Y, Vakhshoorzadeh J, Hermance N, Kuroda T, Parulekar N, Taylor A, Manning A, Campbell J, Ganem N. Whole-genome doubling confers unique genetic vulnerabilities on tumour cells. Nature 2021, 590: 492-497. PMID: 33505027, PMCID: PMC7889737, DOI: 10.1038/s41586-020-03133-3.Peer-Reviewed Original ResearchConceptsWhole-genome doublingUnstable tetraploid cellsAccurate chromosome segregationDNA replication factorsSpindle assembly checkpointPrimary human cancer samplesHuman cancer samplesEssentiality dataChromosome segregationUnique genetic vulnerabilitiesTetraploid stateKinesin proteinsProteasome functionMitotic errorsGenetic traitsTetraploid cellsHuman cancersCancer cell linesCancer cellsCell linesKIF18ACell viabilityCancer samplesHuman tissuesCells
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
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