Life Sciences & Biotechnology
Title : | structural insight regarding the interaction between the processivity clamp and DNA polymerase I in prokaryotes. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Prof. Deepak T Nair, Regional Centre For Biotechnology, Faridabad, Haryana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | deepak@rcb.res.in |
Details
Executive Summary : | DNA polymerase I (dPolI) is a crucial enzyme in prokaryotes that plays a vital role in high-fidelity DNA replication. It has three enzyme activities: 5' to 3' DNA polymerase (POL), 5' to 3' exonuclease (EXO1), and 3' to 5' exonuclease (EXO2). dPol1 is essential for Okazaki fragment maturation, which ensures the organism's survival and propagation. The EXO1 exonuclease activity removes RNA nucleotides from covalently linked primers, while the POL activity performs template-dependent DNA synthesis. The EXO2 activity proofreads newly synthesized DNA. The coordinated function of these enzyme activities ensures high fidelity DNA synthesis, preventing genomic DNA degradation. This activity is critical for survival, as the presence of ribonucleotides in the genome can lead to lethal double-stranded breaks. In addition to Okazaki fragment maturation, dPolI also plays a role in DNA repair pathways like non-homologous end joining. The processivity clamp, a toroid around DNA during replication, forms a toroid around the DNA. However, dPolI does not associate with a specific site on the Clamp due to the absence of known Clamp binding motifs. Using dPolI (Eco-dPolI) and the processivity clamp (Eco-clamp) from Escherichia coli as model proteins, researchers aim to provide structural insight into the interaction between the processivity clamp and DNA polymerase I in prokaryotes. The study will identify peptide regions on dPol1 that associate with the clamp in the presence and absence of substrate DNA. This knowledge can be used in the development of novel antimicrobials against carbapenem-resistant Enterobacteriace family members. |
Total Budget (INR): | 47,09,059 |
Organizations involved