title: Spindle assembly checkpoint inactivation fails to suppress neuroblast tumour formation in aurA mutant Drosophila.
abstract: Tissue homeostasis requires accurate control of cell proliferation, differentiation and chromosome segregation. Drosophila sas-4 and aurA mutants present brain tumours with extra neuroblasts (NBs), defective mitotic spindle assembly and delayed mitosis due to activation of the spindle assembly checkpoint (SAC). Here we inactivate the SAC in aurA and sas-4 mutants to determine whether the generation of aneuploidy compromises NB proliferation. Inactivation of the SAC in the sas-4 mutant impairs NB proliferation and disrupts euploidy. By contrast, disrupting the SAC in the aurA mutant does not prevent NB amplification, tumour formation or chromosome segregation. The monitoring of Mad2 and cyclin B dynamics in live aurA NBs reveals that SAC satisfaction is not coupled to cyclin B degradation. Thus, the NBs of aurA mutants present delayed mitosis, with accurate chromosome segregation occurring in a SAC-independent manner. We report here the existence of an Aurora A-dependent mechanism promoting efficient, timed cyclin B degradation.
authors.affiliation: Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290, 2 avenue du Pr Léon Bernard, 35043 Rennes, France.
authors.forename: Renaud
authors.identifier: http://orcid.org/0000-0002-3521-5250
authors.initials: R
authors.lastname: Caous
authors.affiliation: Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290, 2 avenue du Pr Léon Bernard, 35043 Rennes, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Pascal
authors.affiliation: Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290, 2 avenue du Pr Léon Bernard, 35043 Rennes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Romé
authors.affiliation: Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290, 2 avenue du Pr Léon Bernard, 35043 Rennes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Richard-Parpaillon
authors.affiliation: Institut Jacques Monod-Université Paris Diderot-Paris 7, 15 rue Hélène Brion, 75205 Paris, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Karess
authors.affiliation: Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290, 2 avenue du Pr Léon Bernard, 35043 Rennes, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Giet
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics*; D049109:Cell Proliferation; D020090:Chromosome Segregation; D019926:Cyclin B / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins; D008938:Mitosis; D009154:Mutation; D058953:Neural Stem Cells; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D009474:Neurons
chemical_list: C503698:CycB protein, Drosophila; D019926:Cyclin B; D029721:Drosophila Proteins; D064246:Mad2 Proteins; C577685:Mad2 protein, Drosophila; D008869:Microtubule-Associated Proteins; C522063:Sas-4 protein, Drosophila; D064096:Aurora Kinase A; C576942:aurA protein, Drosophila