Resolution of human ribosomal DNA occurs in anaphase, dependent on tankyrase 1, condensin II, and topoisomerase IIα

  1. Susan Smith1
  1. 1Department of Pathology, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA;
  2. 2Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Ireland
  1. Corresponding author: susan.smith{at}med.nyu.edu
  • 3 Present address: Celgene Corp., Summit, New Jersey 07901, USA.

Abstract

Formation of individualized sister chromatids is essential for their accurate segregation. In budding yeast, while most of the genome segregates at the metaphase to anaphase transition, resolution of the ribosomal DNA (rDNA) repeats is delayed. The timing and mechanism in human cells is unknown. Here we show that resolution of human rDNA occurs in anaphase after the bulk of the genome, dependent on tankyrase 1, condensin II, and topoisomerase IIα. Defective resolution leads to rDNA bridges, rDNA damage, and aneuploidy of an rDNA-containing acrocentric chromosome. Thus, temporal regulation of rDNA segregation is conserved between yeast and man and is essential for genome integrity.

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Footnotes

  • Received October 22, 2018.
  • Accepted January 7, 2019.

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