Biology subjects

Priyadarshini, P.

Publications and source records attributed to Priyadarshini, P..

4 recordsLinked to original sources

bioRxiv2025

Recruitment of Mre11 to recombination sites during meiosis

The Mre11 nuclease, part of the conserved MRX complex involved in the repair of DNA double-strand breaks (DSBs), is also essential to initiate meiotic recombination in budding yeast by promoting Spo11-induced DSBs. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2 (RMM) that organize the meiotic DSB machinery by a mechanism involving biomolecular condensation. Here, we explored the role of Mre11 during meiosis and its relationship to RMM condensation. We show that both Mre11 and MRX complexes form DNA-dependent, hexanediol sensitive condensates in vitro. In vivo, Mre11 assembles into DNA damage-dependent foci in vegetative cells and DSB-independent foci in meiotic cells. In vitro condensates and in vivo foci both depend on the C-terminal intrinsically-disordered region (IDR) of Mre11. Importantly, while the Mre11 IDR is dispensable for vegetative DNA repair it is essential during meiosis. The C-terminus of Mre11 forms a short -helix that binds a conserved region of Mer2, and mutating residues within this interface reduces Mre11 foci and DSB formation. Finally, we identified a SUMO-interacting motif within the Mre11 IDR that enhances recruitment of Mre11 during meiosis and facilitates DSB formation. This work identifies multiple mechanisms that collaborate to recruit Mre11 during meiosis to initiate recombination.

molecular biology↗

bioRxiv2021

Investigating the effect of Ser256 phosphorylation on gating of aquaporin-2: Molecular Dynamics study

Regulation of water transport via aquaporins is crucial for osmoregulation and water homeostasis of an organism. This transport of water is regulated either by gating or trafficking wherein AQPs are transported from intracellular storage sites to plasma membrane. It has been proposed that water movement via AQP2 is regulated by post-translational modification. We aimed to explore the structural and functional changes occurring in AQP2 due to Ser256 phosphorylation. We have carried out molecular dynamics simulations to investigate molecular basis of effect of phosphorylation on water permeability of AQP2. MD simulations show that there are mild variations in the pore sizes of different monomers of the phosphorylated and unphosphorylated AQP2. Analysis of inter and intra-monomeric interactions such as hydrogen bond, electrostatic and hydrophobic interactions has been carried out. Structures of the phosphorylated AQP2 do not show any blocking of mouth of pore of the monomers during the course of MD simulations. Further, water permeability calculations do corroborate the above finding. This molecular dynamics study suggests that phosphorylation of C-terminal Ser-256 residue of AQP2 may not be directly responsible for gating mechanism.

bioinformatics↗

bioRxiv2020

Nanoencapsulation of clove oil and study of physico-chemical properties, cytotoxic, haemolytic and antioxidant activities

The therapeutic properties of clove oil is known for centuries, however, the pungent nature, chemical instability and low water solubility impose limitations in harnessing its therapeutic potential. Hence, nanoencapsulation of clove oil was performed to overcome the above constraints and control its in-vitro release. The stability of nanoemulsion depends on various factors where the surfactant and its hydrophile/lipofile balance (HLB) play a key role. The non-ionic surfactants Tween 20, 40 and 80 with HLB of 16.7, 15.6 and 15, respectively, were used to study the stability of clove oil nanoemulsion (CON). The creaming index of CON prepared with Tween 20, 40 and 80 was 22.75 and 17.5 and 1.5%, respectively, after 8 days of storage at room temperature. Tween 20 and 40 produced particles > 300 nm while Tween 80 resulted in particles of size [~]150 nm. Transmission electron microscopic image of spray dried CON prepared with Tween 80 showed particle size in the range 150-190 nm after one month of storage at room temperature. The in vitro release studies showed 76% and 42% cumulative release of CON and native clove oil (NC), respectively at pH 7.4. The cellular toxicity of CON was significantly reduced by four fold compared to NC at a concentration of 60 {micro}g/mL when tested on Caco2 cells. Similarly, haemolytic activity on red blood cells revealed less than 10% haemolysis signifying the compatibility of CON for its nutraceutical applications. In addition, CON also exhibited higher in-vitro antioxidant compared to NC as shown by DPPH and ABTS radical scavenging activity. Collectively, we have developed a unique method for NC nanoencapsulation using cost effective polysaccharide (maltodextrin) and surfactant for stabilizing the nanoemulsion for increased bioactivity.

cell biology↗

bioRxiv2018

Molecular Complexes for Effective Inhibition of Tau Aggregation

Tau is an axonal protein known to form abnormal aggregates and is the biomarker of Alzheimers disease. Metal-based therapeutics for inhibition of Tau aggregation is limited and rarely reported in the contemporary science. Here, the first example is reported of a rationally designed molecular cobalt(II)-complexes for effective inhibition of Tau and disaggregation of preformed Tau fibrils. The mechanistic studies revealed that the prevention of Tau aggregation by CBMCs is concentration-dependent and Tau seldom exhibits conformational changes. Interestingly, CBMCs play a dual role by causing disassembly of preformed aggregates as well as complete Tau inhibition. We believe that this unprecedented finding by the newly developed molecular complexes has a potential to lead to developing innovative metal-based therapeutics for Alzheimers disease.

neuroscience↗