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RESEARCH PRODUCT

CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly

Daniele FachinettiMoira A. McmahonSebastian HoffmannSolène HervéViviana BarraYael Nechemia-arbelyPeter LyMarie DumontDon W. Cleveland

subject

0301 basic medicineChromosomal Proteins Non-HistoneMedical PhysiologyEpigenesis GeneticChromosome segregationModelsChromosome SegregationKinetochoresGeneticsTumormitosiKinetochorekinetochoreCell biologyChromatinChromosomal Proteinsprotein degradationCENP-ACENP-BepigeneticCENP-C1.1 Normal biological development and functioningKinetochore assemblyCentromerechromosome segregationMitosismacromolecular substancesBiologyProtein degradationModels BiologicalGeneral Biochemistry Genetics and Molecular BiologyArticleCell Line03 medical and health sciencesGeneticUnderpinning researchCentromere Protein ACell Line TumorCentromereGeneticsHumansMitosisNon-HistoneBiologicalSettore BIO/18 - Genetica030104 developmental biologyGeneric health relevanceBiochemistry and Cell BiologyauxinCentromere Protein AEpigenesis

description

SummaryHuman centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation. Without the continuing presence of CENP-A, CENP-B binding to alphoid DNA sequences becomes essential to preserve anchoring of CENP-C and the kinetochore to each centromere. Thus, there is a reciprocal interdependency of CENP-A chromatin and the underlying repetitive centromere DNA sequences bound by CENP-B in the maintenance of human chromosome segregation.

yearjournalcountryeditionlanguage
2016-11-01Cell Reports
10.1016/j.celrep.2016.10.084http://dx.doi.org/10.1016/j.celrep.2016.10.084