title: Cytokinesis breaks dicentric chromosomes preferentially at pericentromeric regions and telomere fusions.
abstract: Dicentric chromosomes are unstable products of erroneous DNA repair events that can lead to further genome rearrangements and extended gene copy number variations. During mitosis, they form anaphase bridges, resulting in chromosome breakage by an unknown mechanism. In budding yeast, dicentrics generated by telomere fusion break at the fusion, a process that restores the parental karyotype and protects cells from rare accidental telomere fusion. Here, we observed that dicentrics lacking telomere fusion preferentially break within a 25- to 30-kb-long region next to the centromeres. In all cases, dicentric breakage requires anaphase exit, ruling out stretching by the elongated mitotic spindle as the cause of breakage. Instead, breakage requires cytokinesis. In the presence of dicentrics, the cytokinetic septa pinch the nucleus, suggesting that dicentrics are severed after actomyosin ring contraction. At this time, centromeres and spindle pole bodies relocate to the bud neck, explaining how cytokinesis can sever dicentrics near centromeres.
authors: Laboratoire Télomères et Réparation du Chromosome, Service Instabilité Génétique Réparation et Recombinaison, Institut de Radiobiologie Moléculaire et Cellulaire, Commissariat à l'Energie Atomique et aux Energies Alternatives, 92265 Fontenay-aux-Roses, France; UMR967, Institut National de la Santé et de la Recherche Médicale, 92265 Fontenay-aux-Roses, France;
authors: Virginia
authors: V
authors: Lopez
authors: Laboratoire Télomères et Réparation du Chromosome, Service Instabilité Génétique Réparation et Recombinaison, Institut de Radiobiologie Moléculaire et Cellulaire, Commissariat à l'Energie Atomique et aux Energies Alternatives, 92265 Fontenay-aux-Roses, France; UMR967, Institut National de la Santé et de la Recherche Médicale, 92265 Fontenay-aux-Roses, France;
authors: Natalja
authors: N
authors: Barinova
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;
authors: Masayuki
authors: M
authors: Onishi
authors: Laboratoire Télomères et Réparation du Chromosome, Service Instabilité Génétique Réparation et Recombinaison, Institut de Radiobiologie Moléculaire et Cellulaire, Commissariat à l'Energie Atomique et aux Energies Alternatives, 92265 Fontenay-aux-Roses, France; UMR967, Institut National de la Santé et de la Recherche Médicale, 92265 Fontenay-aux-Roses, France;
authors: Sabrina
authors: S
authors: Pobiega
authors: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;
authors: John R
authors: JR
authors: Pringle
authors: UMR967, Institut National de la Santé et de la Recherche Médicale, 92265 Fontenay-aux-Roses, France; Laboratoire Instabilité Génétique et Organisation Nucléaire, Service Instabilité Génétique Réparation et Recombinaison, Institut de Radiobiologie Moléculaire et Cellulaire, Commissariat à l'Energie Atomique et aux Energies Alternatives, 92265 Fontenay-aux-Roses, France.
authors: Karine
authors: K
authors: Dubrana
authors: Laboratoire Télomères et Réparation du Chromosome, Service Instabilité Génétique Réparation et Recombinaison, Institut de Radiobiologie Moléculaire et Cellulaire, Commissariat à l'Energie Atomique et aux Energies Alternatives, 92265 Fontenay-aux-Roses, France; UMR967, Institut National de la Santé et de la Recherche Médicale, 92265 Fontenay-aux-Roses, France; stephane.marcand@cea.fr.
authors: Stéphane
authors: S
authors: Marcand
mesh_terms: D048750:Cell Nucleus Division; D002503:Centromere / Q000235:genetics*; D019457:Chromosome Breakage; D015825:Chromosomes, Fungal / Q000235:genetics*; D048749:Cytokinesis; D008938:Mitosis; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D016615:Telomere / Q000378:metabolism*
keywords: cell cycle exit; centromere; chromosome; cytokinesis; telomere
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