title: Impaired manganese metabolism causes mitotic misregulation.
abstract: Manganese is an essential trace element, whose intracellular levels need to be carefully regulated. Mn(2+) acts as a cofactor for many enzymes and excess of Mn(2+) is toxic. Alterations in Mn(2+) homeostasis affect metabolic functions and mutations in the human Mn(2+)/Ca(2+) transporter ATP2C1 have been linked to Hailey-Hailey disease. By deletion of the yeast orthologue PMR1 we have studied the impact of Mn(2+) on cell cycle progression and show that an excess of cytosolic Mn(2+) alters S-phase transit, induces transcriptional up-regulation of cell cycle regulators, bypasses the need for S-phase cell cycle checkpoints and predisposes to genomic instability. On the other hand, we find that depletion of the Golgi Mn(2+) pool requires a functional morphology checkpoint to avoid the formation of polyploid cells.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-CSIC, Sevilla, Spain.
authors.forename: Néstor
authors.initials: N
authors.lastname: García-Rodríguez
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Díaz de la Loza
authors.forename: Bethany
authors.initials: B
authors.lastname: Andreson
authors.forename: Fernando
authors.initials: F
authors.lastname: Monje-Casas
authors.forename: Rodney
authors.initials: R
authors.lastname: Rothstein
authors.forename: Ralf Erik
authors.initials: RE
authors.lastname: Wellinger
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle; D005434:Flow Cytometry; D042822:Genomic Instability; D006706:Homeostasis; D008345:Manganese / Q000378:metabolism*; D008938:Mitosis
chemical_list: D008345:Manganese