A5058230659- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Genetic Neurodegenerative Diseases
- Heat shock proteins research
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Invertebrate Immune Response Mechanisms
- Prion Diseases and Protein Misfolding
- Fungal and yeast genetics research
- Genomics and Rare Diseases
- Computational Drug Discovery Methods
- Ubiquitin and proteasome pathways
- Amyotrophic Lateral Sclerosis Research
- Plant biochemistry and biosynthesis
- Plant Molecular Biology Research
- RNA and protein synthesis mechanisms
- Neurological diseases and metabolism
- DNA Repair Mechanisms
- Biotin and Related Studies
- Nuclear Structure and Function
- RNA regulation and disease
- Coenzyme Q10 studies and effects
Savitribai Phule Pune University
2019-2024
Institute of Bioinformatics
2019-2024
Stowers Institute for Medical Research
2009-2014
Cohesin is a protein complex known for its essential role in chromosome segregation. However, cohesin and associated factors have additional functions transcription, DNA damage repair, condensation. The human cohesinopathy diseases are thought to stem not from defects segregation but gene expression. of expression well understood. We used budding yeast strains bearing mutations analogous the disease alleles under control their native promoter study These do significantly affect...
In Saccharomyces cerevisiae, chromatin is spatially organized within the nucleus with centromeres clustering near spindle pole body, telomeres into foci at nuclear periphery, ribosomal DNA repeats localizing a single nucleolus, and transfer RNA (tRNA) genes present in an adjacent cluster. Furthermore, certain relocalize from interior to periphery upon transcriptional activation. The molecular mechanisms responsible for organization of genome are not well understood. We find that...
The cohesin complex contributes to ribosome function, although the molecular mechanisms involved are unclear. Compromised function is associated with a class of diseases known as cohesinopathies. One cohesinopathy, Roberts syndrome (RBS), occurs when mutation reduces acetylation Smc3 subunit. Mutation acetyltransferase impaired rRNA production, biogenesis, and protein synthesis in yeast human cells. Cohesin binding ribosomal DNA (rDNA) evolutionarily conserved from bacteria We report that...
Eco1 is the acetyltransferase that establishes sister-chromatid cohesion during DNA replication. A budding yeast strain with an eco1 mutation genocopies Roberts syndrome has reduced ribosomal (rDNA) transcription and a transcriptional signature of starvation. We show deleting FOB1--a gene encodes replication fork-blocking protein specific for rDNA region--rescues rRNA production partially rescues genome-wide. Further studies deletion FOB1 corrects genome-wide defects, nucleolar structure,...
Orb2 the Drosophila homolog of cytoplasmic polyadenylation element binding (CPEB) protein forms prion-like oligomers. These oligomers consist Orb2A and Orb2B isoforms their formation is dependent on oligomerization isoform. with a mutation diminishing Orb2A's long-term memory but fails to maintain it over time. Since this plays crucial role in maintenance memory, here, we aim find what regulates oligomerization. In an immunoprecipitation-based screen, identify interactors Hsp40 Hsp70...
Abstract Orb2 the Drosophila homolog of Cytoplasmic polyadenylation element binding protein (CPEB) forms prion-like oligomers. These oligomers consist Orb2A and Orb2B isoforms their formation are dependent on oligomerization isoform. with a mutation diminishing Orb2A’s long-term memory but fails to maintain it over time. Since, this plays crucial role in maintenance memory, here we aim find what regulates oligomerization. In an immunoprecipitation-based screen, identify interactors Hsp40...
<title>Abstract</title> Huntington’s disease (HD) is a rare neurodegenerative caused due to aggregation of Huntingtin (HTT) protein. This study involves cloning 40 DnaJ chaperones from Drosophila, and overexpressing them in yeasts fly models HD. Accordingly, were catalogued as enhancers or suppressors based on their growth phenotypes properties. 2 the that came up targets CG5001 P58IPK. Protein slow phenotype was rescued yeasts, S2 cells, Drosophila transgenic lines HTT103Q with these...
Abstract The cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and condensation. Mutations proteins give rise to disease collectively referred as Cohesinopathies. major cause of Cohesinopathies arise due defects associated with gene expression, that developmental disorders. In this study, we have used Saccharomyces cerevisiae mimic the Cohesinopathy disorder Roberts syndrome mutations ( eco1W216G ) homologous humans (esco2). Our...
Amyotrophic lateral Sclerosis (ALS) is an adult-onset neurogenerative disease. It affects the motor neurons resulting in muscle weakness and causing death of patient. Multiple factors like genetic, environmental, as well age involved etiopathogenesis ALS. ALS a highly complex equally challenging disease that involves various pathogenesis linked with progressive neuron degeneration, it difficult to have single therapeutic target against Till date only few drugs been FDA-approved, while many...
Abstract Huntington’s disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While Htt amyloid aggregates are known to affect many cellular processes, its role translation not addressed. Here we report pathogenic expression causes protein synthesis deficit cells. We find functional prion-like protein, regulator Orb2 be sequestered aggregates. Coexpression of can partially rescue lethality associated with expanded Htt. These...
Roberts Syndrome (RBS) is an autosomal recessive disease characterized by prenatal growth retardation caused mutations in the cohesin acetyltransferase ESCO2 gene. Previously we revealed that human impaired ribosomal RNA production and protein synthesis. We recently observed mTOR (mammalian target of rapamycin) signaling was strongly downregulated RBS cells. Stimulation pathway with L‐leucine helped to partially rescue both synthesis cell proliferation. To further address transcriptional...
Abstract Huntington’s disease (HD) is a rare neurodegenerative disease. It caused due to aggregation of Huntingtin (HTT) protein containing Q repeats more than 40. Similar also hallmark several other diseases related loss cognitive function. In search modifiers HTT aggregation, we have screened putative chaperone proteins from Drosophila in both fly and yeast model HD. DnaJ chaperones were by evaluating phenotypes using growth assays for studying the rate cells, imaging studies, gel-based...