1. Developmental Biology
  2. Chromosomes and Gene Expression
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Distinct responses to reduplicated chromosomes require distinct Mad2 responses

  1. Benjamin M Stormo
  2. Donald T Fox  Is a corresponding author
  1. Duke University Medical Center, United States
Research Article
  • Cited 14
  • Views 1,621
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Cite this article as: eLife 2016;5:e15204 doi: 10.7554/eLife.15204


Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindle-independent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2's control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention.

Article and author information

Author details

  1. Benjamin M Stormo

    Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Donald T Fox

    Department of Cell Biology, Duke University Medical Center, Durham, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Yukiko M Yamashita, University of Michigan, United States

Publication history

  1. Received: February 12, 2016
  2. Accepted: May 8, 2016
  3. Accepted Manuscript published: May 9, 2016 (version 1)
  4. Version of Record published: June 8, 2016 (version 2)


© 2016, Stormo & Fox

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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