4.7 Article

Cytokinesis breaks dicentric chromosomes preferentially at pericentromeric regions and telomere fusions

Journal

GENES & DEVELOPMENT
Volume 29, Issue 3, Pages 322-336

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.254664.114

Keywords

cell cycle exit; centromere; chromosome; cytokinesis; telomere

Funding

  1. National Institutes of Health Shared Instrumentation [1S10RR02678001]
  2. Association pour la Recherche sur le Cancer (ARC)
  3. Agence Nationale de la Recherche (ANR) [Blanc-SVSE-8-2011-TELODICENs]
  4. CEA-IRTELIS Ph.D. program
  5. ARC

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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.

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