title: Epigenetic centromere specification directs aurora B accumulation but is insufficient to efficiently correct mitotic errors.
abstract: The nearly ubiquitous presence of repetitive centromere DNA sequences across eukaryotic species is in paradoxical contrast to their apparent functional dispensability. Centromeric chromatin is spatially delineated into the kinetochore-forming array of centromere protein A (CENP-A)-containing nucleosomes and the inner centromeric heterochromatin that lacks CENP-A but recruits the aurora B kinase that is necessary for correcting erroneous attachments to the mitotic spindle. We found that the self-perpetuating network of CENPs at the foundation of the kinetochore is intact at a human neocentromere lacking repetitive alpha-satellite DNA. However, aurora B is inappropriately silenced as a consequence of the altered geometry of the neocentromere, thereby compromising the error correction mechanism. This suggests a model wherein the neocentromere represents a primordial inheritance locus that requires subsequent generation of a robust inner centromere compartment to enhance fidelity of chromosome transmission.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Bassett
authors.forename: Stacey
authors.initials: S
authors.lastname: Wood
authors.forename: Kevan J
authors.initials: KJ
authors.lastname: Salimian
authors.forename: Sandya
authors.initials: S
authors.lastname: Ajith
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Foltz
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001324:Autoantigens / Q000378:metabolism; D002478:Cells, Cultured; D002503:Centromere / Q000235:genetics* / Q000378:metabolism; D000076247:Centromere Protein A; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases