Impaired manganese metabolism causes mitotic misregulation.
J Biol Chem, 2012/5/25;287(22):18717-29.
García-Rodríguez N[1], Díaz de la Loza Mdel C, Andreson B, Monje-Casas F, Rothstein R, Wellinger RE
Affiliations
PMID: 22493290DOI: 10.1074/jbc.M112.358309
Impact factor: 5.486
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.
MeSH terms
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download