Suchergebnisse

10 páginas, 5 figuras ; Adaptation to environmental changes is crucial for cell fitness. In Saccharomyces cerevisiae, variations in external osmolarity trigger the activation of the stress-activated protein kinase Hog1 (high-osmolarity glycerol 1), which regulates gene expression, metabolism, and cell-cycle progression. The activation of this kinase leads to the regulation of G1, S, and G2 phases of the cell cycle to prevent genome instability and promote cell survival. Here we show that Hog1 delays mitotic exit when cells are stressed during metaphase. Hog1 phosphorylates the nucleolar protein Net1, altering its affinity for the phosphatase Cdc14, whose activity is essential for mitotic exit and completion of the cell cycle. The untimely release of Cdc14 from the nucleolus upon activation of Hog1 is linked to a defect in ribosomal DNA (rDNA) and telomere segregation, and it ultimately delays cell division. A mutant of Net1 that cannot be phosphorylated by Hog1 displays reduced viability upon osmostress. Thus, Hog1 contributes to maximizing cell survival upon stress by regulating mitotic exit. ; S.T. was the recipient of a contract for Investigador Doctor Junior (PDJ 2014, Generalitat de Catalunya) and a Juan de la Cierva fellowship. The study was supported by grants from the Spanish Ministry of Economy and Competitiveness (PGC2018-094136-B-I00 to F.P.; BFU2017-85152-P and FEDER to E.d.N.; BFU2016-77975-R and FEDER to E.Q.), the Catalan Government (2017 SGR 799), and Fundación Botín, by Banco Santander through its Santander Universities Global Division (to F.P.). We gratefully acknowledge institutional funding from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) through the Centres of Excellence Severo Ochoa Award, and from the CERCA Programme of the Catalan Government and the Unidad de Excelencia María de Maeztu, funded by the AEI (CEX2018-000792-M). F.P. is the recipient of an ICREA Acadèmia Award (Generalitat de Catalunya). ; Peer reviewed