Biology subjects

Caydasi, A. K.

Publications and source records attributed to Caydasi, A. K..

4 recordsLinked to original sources

bioRxiv2025

Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in Saccharomyces cerevisiae

The Yippee-like (YPEL) proteins are a conserved eukaryotic gene family implicated in proliferation, senescence, and stress adaptation. In humans, five paralogs (YPEL1-YPEL5) are widely expressed and encode proteins with high sequence and amino acid similarity, yet the molecular basis of their functions remains poorly defined. While conservation implies possible functional redundancy, the distinct roles of each YPEL paralog have not been defined. The budding yeast S. cerevisiae possesses a single ortholog, MOH1, which contributes to survival and stress responses and can be functionally complemented by human YPELs. However, the cellular role of MOH1 remains to be elucidated. Here, we investigated the function of MOH1 in S. cerevisiae. MOH1 deletion (moh1{Delta}) conferred sensitivity to sodium azide and sulfuric acid but increased resistance to hydrogen peroxide and acetic acid. Moh1 protein levels decreased upon hydrogen peroxide treatment and increased following sulfuric acid exposure, indicating stress-dependent regulation. Light and scanning electron microscopy showed that moh1{Delta} cells are constitutively rounder, tend to form clumps, and exhibit rough surface features, indicating altered cellular architecture. RNA profiling and FTIR spectroscopy revealed transcriptional reprogramming and metabolic remodeling in moh1{Delta} cells, including alterations in lipid, protein, and cell wall polysaccharide levels and composition. Intracellular ROS assays indicated that hydrogen peroxide resistance can be attributed to decreased cellular uptake resulting from altered permeability, rather than changes in mitochondrial ROS production. Collectively, our findings identify Moh1 as a regulatory factor linking gene expression to metabolism and cellular architecture, influencing membrane permeability and conferring selective stress resistance in S. cerevisiae.

cell biology↗

bioRxiv2024

PI(3,5)P2 asymmetry during mitosis is essential for asymmetric vacuolar inheritance

Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is a low-abundance signaling lipid that plays crucial roles in various cellular processes, including endolysosomal system structure/function, stress response, and cell cycle regulation. PI(3,5)P2 synthesis increases in response to environmental stimuli, yet its behavior in cycling cells under basal conditions remained elusive. Here, we analyzed spatiotemporal changes in PI(3,5)P2 levels during the cell cycle of S. cerevisiae. We found that PI(3,5)P2 accumulates on the vacuole in the daughter-cell while it disappears from the vacuole in the mother-cell during mitosis. Concomitant with the changes in PI(3,5)P2 distribution, the daughter-vacuole became more acidic, whereas the acidity of the mother-vacuole decreased during mitosis. Our data further showed that both PI(3,5)P2 and the PI(3,5)P2 effector protein Atg18 are determinants of vacuolar-pH asymmetry and acidity. Our work, thus, identifies PI(3,5)P2 as a key factor for establishment of vacuolar-pH asymmetry, providing insights into how the mother cell ages while the daughter cell is rejuvenated.

cell biology↗

bioRxiv2020

Protein Phosphatase 1 in association with Bud14 inhibits mitotic exit in Saccharomyces cerevisiae

Mitotic exit in budding yeast is dependent on correct orientation of the mitotic spindle along the cell polarity axis. When accurate positioning of the spindle fails, a surveillance mechanism named the Spindle Position Checkpoint (SPOC) prevents cells from exiting mitosis. Mutants with a defective SPOC become multinucleated and lose their genomic integrity. Yet, a comprehensive understanding of the SPOC mechanism is missing. In this study, we identified the type 1 protein phosphatase, Glc7, in association with its regulatory protein Bud14 as a novel checkpoint component. We further showed that Glc7-Bud14 promotes dephosphorylation of the SPOC effector protein Bfa1. Our results suggest a model in which two mechanisms act in parallel for a robust checkpoint response: first, the SPOC kinase Kin4 isolates Bfa1 away from the inhibitory kinase Cdc5 and second, Glc7-Bud14 dephosphorylates Bfa1 to fully activate the checkpoint effector.

cell biology↗

bioRxiv2019

SWR1 Chromatin Remodeling Complex Prevents Mitotic Slippage during Spindle Position Checkpoint Arrest

Faithful chromosome segregation in budding yeast requires correct positioning of the mitotic spindle along the mother to daughter cell polarity axis. When the anaphase spindle is not correctly positioned, a surveillance mechanism, named as the spindle position checkpoint (SPOC), prevents the progression out of mitosis until correct spindle positioning is achieved. How SPOC works on a molecular level is not well-understood. Here, we performed a genome-wide genetic screen to search for components required for SPOC. We identified the SWR1 chromatin-remodeling complex (SWR1-C) among the several novel factors that are essential for SPOC integrity. Cells lacking SWR1-C were able to activate SPOC upon spindle misorientation but underwent mitotic slippage upon prolonged SPOC arrest. This mitotic slippage required the Cdc14-early anaphase release pathway and other factors including the SAGA histone acetyltransferase complex, proteasome components, the mitotic cyclin-dependent kinase inhibitor Sic1 and the mitogen-activated protein kinase Slt2/Mpk1. Together, our data establish a novel link between chromatin remodeling and robust checkpoint arrest in late anaphase. AUTHORS SUMMARYBefore it physically divides into two, the cell must duplicate its genetic material and separate the duplicated copies to the opposite poles of the cell with the help of the spindle machinery. The direction along which the genetic material is separated has different consequences on cell division, especially when the opposite poles of the cell differ from each other, as is the case of asymmetric cell division. Every cell division in budding yeast is asymmetric. The new (daughter) cell grows on the old (mother) cell and pinches of from this location at the end of the cell division, giving rise to a new and an old cell. The daughter and mother cells differ in size and composition, thus the cell division is asymmetric. In order for the daughter cell to receive one copy of the duplicated genetic material, budding yeast has to separate the copies of its genetic material along the mother to daughter cell direction, which is possible by placing the spindle apparatus along this direction. A surveillance mechanism named the Spindle Position Checkpoint (SPOC) in budding yeast monitors the position of the mitotic spindle and prevents cells from dividing if the spindle fails to align in the mother to daughter direction. The cell can resume cell division only after correcting the position of the spindle followed by inactivation of SPOC. This way SPOC prevents multi-nucleation and enucleation, and hence it is a crucial mechanism to maintain the correct ploidy. It has been known that about five proteins play a role in positively supporting the SPOC. Yet, how SPOC works on a molecular level remains ill understood. In this study, we aimed to find out novel components of SPOC. Through an unbiased genome-wide genetic screen, we successfully identified several new components of the SPOC machinery. Among several other novel proteins identified, we investigated the role of the SWR1 chromatin remodeling complex (SWR1-C) in more detail. We show that the SWR1-C has a function in preventing cells with mis-positioned spindles from resuming cell division when the spindle stays mis-positioned for a prolonged time (mitotic slippage). Our data indicated that SWR1-C is not required to start the immediate SPOC response, rather it is important to keep the prolonged SPOC arrest.

cell biology↗