title: Mitotic catenation is monitored and resolved by a PKCε-regulated pathway.
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.
authors.affiliation: Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincolns Inn Fields, London WC2A 3LY, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Brownlow
authors.affiliation: Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincolns Inn Fields, London WC2A 3LY, UK.
authors.forename: Tanya
authors.initials: T
authors.lastname: Pike
authors.affiliation: Light Microscopy, Cancer Research UK London Research Institute, London, WC2A 3LY, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zicha
authors.affiliation: Electron Microscopy, Cancer Research UK London Research Institute, London WC2A 3LY, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Collinson
authors.affiliation: 1] Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincolns Inn Fields, London WC2A 3LY, UK [2] Division of Cancer Studies, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002469:Cell Separation; D020090:Chromosome Segregation; D002875:Chromosomes / Q000648:ultrastructure; D004398:Dyneins / Q000378:metabolism; D005434:Flow Cytometry; D016195:G2 Phase; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008677:Metaphase; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009369:Neoplasms / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012854:Sister Chromatid Exchange; D008941:Spindle Apparatus
chemical_list: D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon; D004398:Dyneins