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14 páginas, 4 figuras. ; During evolution, cells have developed a plethora of mechanisms to optimize survival in a changing and unpredictable environment. In this regard, they have evolved networks that include environmental sensors, signaling transduction molecules and response mechanisms. Hog1 (yeast) and p38 (mammals) stress-activated protein kinases (SAPKs) are activated upon stress and they drive a full collection of cell adaptive responses aimed to maximize survival. SAPKs are extensively used to learn about the mechanisms through which cells adapt to changing environments. In addition to regulating gene expression and metabolism, SAPKs control cell cycle progression. In this review, we will discuss the latest findings related to the SAPK-driven regulation of mitosis upon osmostress in yeast. ; The study was supported by grants from the Spanish Ministry of Economy and Competitiveness (PGC2018-094136-B-I00 to F. Posas; BFU2017-85152-P and FEDER to E. de Nadal; BFU2016-77975-R and FEDER to E. Queralt) and the Catalan Government (2017 SGR 799). 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. Posas is recipient of an ICREA Academia Award (Catalan Government). ; Peer reviewed

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

Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit's complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined. ; [Author Summary] Synthetic biological circuits have been built for different purposes. Nevertheless, the way these devices have been designed so far present several limitations: complex genetic engineering is required to implement complex circuits, and once the parts are built, they are not reusable. We proposed to distribute the computation in several cellular consortia that are physically separated, thus ensuring implementation of circuits independently of their complexity and using reusable components with minimal genetic engineering. This approach allows an easy implementation of multicellular computing devices for secretable inputs or biosensing purposes. ; This work was supported by an ERC Advanced Grant Number 294294 from the EU seventh framework program (SYNCOM) to RS and FP, and the Santa Fe Institute to RS. FP and RS laboratories are also supported by Fundación Botín, by Banco Santander through its Santander Universities Global Division. The laboratory of FP and EdN is supported by grants from the Spanish Government (BFU2012-33503/ BFU2015-64437 P and FEDER to FP; BFU2014-52333-P and FEDER to EdN) and the Catalan Government (2014 SGR 599). The research leading to these results has received funding from "la Caixa" Foundation in collaboration with "Centre per a la Innovació de la Diabetis Infantil Sant Joan de Déu (CIDI)". FP and EdN are recipients of an ICREA Acadèmia (Generalitat de Catalunya). RM was a former EMBO postdoctoral fellow. AU is a recipient of a "La Caixa" fellowship. ; Peer reviewed

15 páginas, 11 figuras. El fichero contiene una rectificación en la página 17 ; The control of mRNA biogenesis is exerted at several steps. In response to extracellular stimuli, stress-activated protein kinases (SAPK) modulate gene expression to maximize cell survival. In yeast, the Hog1 SAPK plays a key role in reprogramming the gene expression pattern required for cell survival upon osmostress by acting during transcriptional initiation and elongation. Here, we genetically show that an intact nuclear pore complex is important for cell survival and maximal expression of stress-responsive genes. The Hog1 SAPK associates with nuclear pore complex components and directly phosphorylates the Nup1, Nup2, and Nup60 components of the inner nuclear basket. Mutation of those factors resulted in a deficient export of stress-responsive genes upon stress. Association of Nup1, Nup2, and Nup60 to stress-responsive promoters occurs upon stress depending on Hog1 activity. Accordingly, STL1 gene territory is maintained at the nuclear periphery upon osmostress in a Hog1-dependent manner. Cells containing non-phosphorylatable mutants in Nup1 or Nup2 display reduced expression of stress-responsive genes. Together, proper mRNA biogenesis of stress-responsive genes requires of the coordinate action of synthesis and export machineries by the Hog1 SAPK ; This work was supported by MINECO (Spanish government) Grant BFU2012-33503, the Consolider Ingenio 2010 program (Grant CSD2007-0015), the Fundación Marcelino Botín (to F. P.), and Grant BFU2011-26722 (to E. d. N.). Recipients of an ICREA Acadèmia (Generalitat de Catalunya). Supported by the MINECO Grant BFU2011-23418. Supported by Agence Nationale de la Recherche (Nucleopol and ODynRib-Jeune chercheur program) and Jeune équipe from Fondation pour la Recherche Médicale. ; Peer reviewed