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Mitotic catenation is monitored and resolved by a PKCε-regulated pathway

Author

Listed:
  • Nicola Brownlow

    (Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute)

  • Tanya Pike

    (Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute)

  • Daniel Zicha

    (Light Microscopy, Cancer Research UK London Research Institute)

  • Lucy Collinson

    (Electron Microscopy, Cancer Research UK London Research Institute)

  • Peter J. Parker

    (Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute
    King’s College London)

Abstract

Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKCε. The PKCε-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained catenation and this delayed exit is characterized by BubR1-high and Mad2-low kinetochores. In addition, we show that this pathway is necessary to facilitate resolution of retained catenanes in mitosis. When delayed by catenation in mitosis, inhibition of PKCε results in premature entry into anaphase with PICH-positive strands and chromosome bridging. These findings demonstrate the importance of PKCε-mediated regulation in protection from loss of chromosome integrity in cells failing to resolve catenation in G2.

Suggested Citation

  • Nicola Brownlow & Tanya Pike & Daniel Zicha & Lucy Collinson & Peter J. Parker, 2014. "Mitotic catenation is monitored and resolved by a PKCε-regulated pathway," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6685
    DOI: 10.1038/ncomms6685
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    Cited by:

    1. Silvia Martini & Khalil Davis & Rupert Faraway & Lisa Elze & Nicola Lockwood & Andrew Jones & Xiao Xie & Neil Q. McDonald & David J. Mann & Alan Armstrong & Jernej Ule & Peter J. Parker, 2021. "A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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