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

• Published in: Nature communications 2014-12, Vol.5 (1), p.5685-5685, Article 5685
• Main Authors: Brownlow, Nicola, Pike, Tanya, Zicha, Daniel, Collinson, Lucy, Parker, Peter J.
• Format: Article
• Language: English
• Subjects: 631/80/641/1655; 631/80/86; Cell Cycle Proteins - metabolism; Cell Separation; Chromosome Segregation; Chromosomes - ultrastructure; Dyneins - metabolism; Flow Cytometry; G2 Phase; Gene Silencing; Green Fluorescent Proteins - metabolism; HEK293 Cells; HeLa Cells; Humanities and Social Sciences; Humans; Kinetochores - metabolism; Metaphase; Microscopy, Fluorescence; Mitosis; multidisciplinary; Neoplasms - metabolism; Protein Kinase C-epsilon - metabolism; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Sister Chromatid Exchange; Spindle Apparatus
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6685

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. Cells are protected from cell division errors by a pathway that detects mitotic catenation. Here, Brownlow et al. show that protein kinase Cε functions in this pathway to drive decatenation, while delaying silencing of the spindle assembly checkpoint to allow time for catenation resolution.