Life Sciences & Biotechnology
Title : | Understanding the plasticity of diverse cohesin complexes during mitosis and meiosis |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Cell Biology, Genetics |
Principal Investigator : | Dr. Mridula Nambiar, Indian Institute of Science Education and Research (IISER) Pune, Maharashtra |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | mridula@iiserpune.ac.in |
Details
Executive Summary : | Cohesins are conserved ring-shaped complexes with four subunits that maintain chromosomal segregation fidelity, transcription, nuclear genome organization, and DNA repair. In mammalian cells, the cohesin complex consists of SMC1α, SMC3, RAD21, and STAG1/2 in somatic cells, while meiosis-specific paralogs SMC1β, REC8/Rad21L, and STAG3 either replace or co-exist with mitotic counterparts in germ cells during meiosis. The evolutionary purpose of having multiple paralogs of the same cohesin protein is unclear, necessitating further understanding of their structure-function relationship. Differently composed cohesin complexes localize to different genomic loci to perform specific functions. In diseases like cancers, aberrant expression of meiosis-specific cohesins appears to play critical roles in causing genomic instability.
This study proposes systematically studying the functional plasticity of mitotic and meiotic cohesin paralogs using Schizosaccaromyces pombe, a powerful model for studying cohesin biology and cell division due to its mechanistic conservation in humans. Strains containing the four different kleisin (Rad21, Rec8) and SA protein (Psc3, Rec11) subunits will be generated, and their functional replaceability and consequences on fundamental cellular processes will be tested. The humanized S. pombe model for cohesin complexes will be used to expand our understanding of cohesin regulation and study the molecular action of frequent mutations seen in patients of cohesinopathies and cancers. A better understanding of the functional roles played by aberrantly expressed meiosis-specific cohesin complexes in somatic cells will have a significant impact on developing targeted chemotherapy strategies against multiple cancer subtypes in the near future. |
Total Budget (INR): | 50,84,970 |
Organizations involved