Research

Life Sciences & Biotechnology

Title :

G-quadruplex structures and their role in genome stability and cancer

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Saurabh Raj, Indian Institute Of Technology (IIT) Delhi

Timeline Start Year :

2022

Timeline End Year :

2024

Contact info :

Equipments :

Details

Executive Summary :

G-quadruplexes, non-canonical structures found in DNA/RNA sequences with high GC content, have been identified as a potential therapeutic target for cancer treatment. They are more readily available in telomere regions and proto-oncogene promoters, making them an important DNA structure for investigation. Over 300,000 sequences likely form G4s in the human genome, many of which occur in functional genomic areas like gene promoters, untranslated regions (UTRs), and hotspots of mutations in DNA. G4s are not easily resolved by most helicases and polymerases, creating a roadblock for replication and transcription. G4-interacting proteins can be categorized into three types: G4 unwinding proteins, G4 stabilizing proteins, and G4 binding proteins. Mutations in these proteins can lead to modification of G4 structures, influencing biological pathways. Understanding the stability of G4 and their affinity with interacting proteins, both in wild-type and mutated forms, is crucial. To use G4 as a kinetic trap in cancerous cells, their structure needs to stabilize against helicases and various buffer conditions. Using magnetic tweezers (MT), it is possible to calculate the precise time it takes for G4 to be resolved by an enzyme or measure their stability under biologically relevant forces and buffer conditions. This single-molecule (SM) technique allows us to mimic the mechanical conditions in which biomolecules are present inside our bodies, enabling real-time observation of individual enzyme behavior and measuring distribution and time-dependent pathways of chemical reactions and biochemical interactions.

Total Budget (INR):

28,71,000

Organizations involved