Life Sciences & Biotechnology
Title : | Role of poly(ADP-ribosyl)ation reaction in telomere length homeostasis |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Utpal Ghosh, University Of Kalyani, West Bengal |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | utpal8ghosh@gmail.com |
Equipments : | UPs with battery backup
Verticle gel apparatus
Refrigerator system
Western blot transfer apparatus |
Details
Executive Summary : | Poly(ADP-ribose) polymerase (PARP) is a key player in DNA repair, apoptosis, cell cycle regulation, angiogenesis, and metastasis. some PARPi have shown promising results against various cancers in clinical trials. However, the details of the regulation of the cellular process by PARylation reaction are still unclear. Proteins involved in telomere length homeostasis are also PARylated, but their biological significance is still unknown. Telomere length (TL) is shortened after each round of replication for linear chromosomes, and replenishment of telomere erosion occurs through telomerase enzymes or a recombination-based process called Alternating Lengthening of Telomere or ALT pathway. Targeting telomerase or ALT pathway is a well-known target in cancer therapy. Previous reports have shown that inhibition of PARylation of hTERT subunit of telomerase by inhibition of PARP reduced telomerase activity. A preliminary study showed that olaparib (PARPi) treatment increased hTERT expression but decreased telomerase activity, suggesting that hTERT expression is not correlated with telomerase activity but PARylation of hTERT matters. There is no correlation between PARylation of other subunits of telomerase with its activity. systematically, the PARylation of each subunit of telomerase and its correlation with telomerase activity will be studied using standard IP and western blot. The TRF2 domain of TRF2 is PARylated by PARP1 and the same domain is the site of interaction of sLX4, a structure-specific endonuclease that performs recombination-based DNA repair and telomere sister chromatid exchange. The study of PARylation reaction on different telomeric proteins and its effect on TL maintenance pathway could help identify the target for cancer therapy. |
Total Budget (INR): | 32,99,538 |
Organizations involved