Biology subjects

Acosta, I.

Publications and source records attributed to Acosta, I..

4 recordsLinked to original sources

bioRxiv2025

Polo-like kinase Cdc5 orchestrates Cdk1 regulation via Swe1 and Mih1 during meiotic prophase I exit

Defects in chromosome synapsis and meiotic recombination activate a checkpoint that, in budding yeast, delays exit from meiotic prophase I by inhibiting the Ndt80-dependent expression of regulators including the cyclin CLB1 and the polo-like kinase (PLK) CDC5. Additionally, Swe1-mediated inhibitory phosphorylation of cyclin-dependent kinase 1 (Cdk1/Cdc28) reinforces this arrest. Once the checkpoint is released, Cdk1 activation is essential for meiosis I entry and requires removal of inhibitory phosphorylation on tyrosine 19, governed by the opposing activities of the Swe1 kinase and the Mih1 phosphatase. Here, we dissect how this network is rewired at the prophase I to meiosis I transition. We show that Swe1 is essential for checkpoint maintenance, but not for its initial activation. We also demonstrate that Cdc5 promotes Cdk1 activation through a dual mechanism: by inducing Swe1 degradation and facilitating Mih1 nuclear translocation. Unlike in mitosis, Cdc5-dependent Swe1 degradation in meiosis does not require CDK-mediated priming and can occur when both proteins are artificially colocalized, indicating a distinct regulatory mode. Our findings uncover a novel function for Cdc5 in promoting meiotic cell cycle progression beyond its known roles in recombination and synaptonemal complex disassembly, highlighting how conserved cell cycle regulators are adapted to meiosis.

cell biology↗

bioRxiv2025

Nucleolar Cdc14 Splitting Reflects Recombination Context and Meiotic Chromosome Dynamics

Chromosome dynamics, recombination, and nucleolar organization intersect during meiotic prophase I, yet how recombination context influences nucleolar architecture remains unclear. We analyzed the nucleolar pool of Cdc14 in Saccharomyces cerevisiae under matched prophase-I gating. In a recombination-competent reference (ndt80{Delta}), Cdc14-mCherry formed a predominant single focus with occasional, reversible two-focus episodes that Nop56-GFP placed within the nucleolar compartment ("nucleolar splitting"). Splitting rose sharply in dmc1{Delta} ndt80{Delta} and remained high in spo11-y135f dmc1{Delta} ndt80{Delta}, demonstrating that elevated DSB formation is not required and pointing instead to homolog-engagement state as the key variable. Population checkpoint readouts did not map onto the phenotype: Hop1 phosphorylation was strong in dmc1{Delta}, weak/transient in ndt80{Delta}, and undetectable in spo11-y135f, yet splitting was high in dmc1{Delta} and spo11-y135f and low in ndt80{Delta}. Persistence metrics showed that events concentrated early and waned in ndt80{Delta}, whereas dmc1{Delta} and spo11 backgrounds retained activity into later windows, consistently across thresholds. We propose that nucleolar splitting reflects rheological responses of a nucleolar condensate to chromosome-scale forces that vary with homolog engagement. This view is consistent with DSB-independent contributions from telomere clustering into the bouquet configuration, telomere-led rapid prophase movements, and centromere coupling/pairing as routes that shape force transmission to the rDNA territory. In this sense, the nucleolus emerges as a mesoscale, mechanically sensitive readout of meiotic chromosome dynamics.

genetics↗

bioRxiv2024

IFI207, a young and fast-evolving protein, controls retroviral replication via the STING pathway

Mammalian AIM-2-like receptor (ALR) proteins bind nucleic acids and initiate production of type I interferons or inflammasome assembly, thereby contributing to host innate immunity. In mice, the Alr locus is highly polymorphic at the sequence and copy number level and we show here, is one of the most dynamic regions of the genome. One rapidly evolving gene within this region, Ifi207, was introduced to the Mus genome by gene conversion or an unequal recombination event a few million years ago. Ifi207 has a large, distinctive repeat region that differs in sequence and length among Mus species and even closely related inbred Mus musculus strains. We show that IFI207 controls MLV infection in vivo and that it plays a role in the STING-mediated response to cGAMP, dsDNA, DMXXA and MLV. IFI207 binds to STING and inclusion of its repeat region appears to stabilize STING protein. The Alr locus and Ifi207 provide a clear example of the evolutionary innovation of gene function, possibly as a result of host-pathogen co-evolution. IMPORTANCEThe Red Queen hypothesis predicts that the arms race between pathogens and the host may accelerate evolution of both sides, and therefore cause higher diversity in virulence factors and immune-related proteins, respectively (1). The Alr gene family in mice has undergone rapid evolution in the last few million years and includes the creation of two novel members, MndaL and Ifi207. Ifi207 in particular became highly divergent, with significant genetic changes between highly related inbred mice. IFI207 protein acts in the STING pathway and contributes to anti-retroviral resistance via a novel mechanism. The data show that under the pressure of host-pathogen coevolution in a dynamic locus, gene conversion and recombination between gene family members creates new genes with novel and essential functions that play diverse roles in biological processes.

immunology↗

bioRxiv2022

High robustness of cytosolic glutathione redox potential under combined salt and osmotic stress in barley as revealed by the biosensor Grx1-roGFP2

O_LIBarley is a staple crop of major global importance and relatively resilient to a wide range of stress factors in the field. Transgenic reporter lines to investigate physiological parameters during stress treatments remain scarce. C_LIO_LIWe generated and characterized stable homozygous barley lines (cv. Golden Promise Fast) expressing the genetically-encoded biosensor Grx1-roGFP2, which indicates the redox potential of the major antioxidant glutathione in the cytosol. C_LIO_LIOur results demonstrate functionality of the sensor in living barley plants. We determined the glutathione redox potential (EGSH) of the cytosol to be in the range of -308 to -320 mV. EGSH was robust against a combined NaCl (150 mM) and water deficit treatment (-0.8 MPa) that caused growth retardation and showed only a minor oxidation after 96 h of treatment. C_LIO_LIWe conclude that the generated reporter lines are a novel resource to study stress resilience in barley. C_LI One sentence summaryGeneration and characterization of barley plants stably expressing Grx1-roGFP2 reveal high robustness of cytosolic glutathione redox potential (EGSH) under combined salt and osmotic stress.

plant biology↗