Moved to IISER Pune

Structure and dynamics of nucleic acid binding proteins

DNA is a remarkably versatile biological device: not only can it store information but in its role as a data-processor, it receives input from a huge variety of compounds that report to it from both inside and outside the cell. While DNA has limited vulnerabilities, with this absence of a robust firewall it is inevitable that it faces persistent threats and damage from vast numbers of malicious molecules (e.g. photosensitizers, hydrogen peroxide, singlet oxygen). The genome's ongoing integrity requires a dedicated team of service proteins that monitor DNA health round-the-clock, and carry out highly specialized repair tasks. Our group is primarily focused on: identifying the molecules that are most threatening to DNA, determining the DNA sites that they attack, and clarifying the parts of certain repair enzymes (base excision repair- BER - glycosylases) that bind to corresponding sites of damaged DNA. Our approaches are both experimental and computational. Experimentally, we reply on the cutting-edge capabilities of our lab's purpose-built UV Resonance Raman (RSS) spectroscopy facility. Using only low-energy radiation, and exploiting the fact that every molecule has a unique spectral fingerprint, RSS is singularly suited to the artefact-free detection of biological molecules. Starting with solutions of selected DNA fragments (nucleobases) mixed either with candidate damaging agents or with normal/mutagenized BER enzymes, then the detection (or not) of complexes of DNA and the molecules-of-interest elegantly addresses all three of our research questions. To clarify the binding-site structure of BER enzymes, we are also modeling these sites computationally. Beyond its fundamental importance, our research on DNA damage and repair will also guide the development of treatments that harness the DNA-damaging potential of intracellular compounds against targeted cells, for example in the treatment of cancer.


    Spriha Gogia, Hemalatha Balaram and Mrinalini Puranik. (2011). HGPRT Distorts the Purine Ring of Nucleotide Substrates and Perturbs pKa of Bound Xanthosine monophosphate. Biochemistry, DOI: 10.1021/bi102039b.

    Namrata Jayanth and Mrinalini Puranik. (2011). Methylation Stabilizes the Imino Tautomer of dAMP and Amino Tautomer of dCMP in Solution. Journal of Physical Chemistry B, DOI: 10.1021/jp200185k.

    Marudachalam Shanmugasundaram and Mrinalini Puranik. (2009). Review. Computational Prediction of Vibrational Spectra of Normal and Modified DNA Nucleobases. Journal of Raman Spectroscopy, 40 (12): 1726-1748.

    Spriha Gogia, Ankur Jain and Mrinalini Puranik. (2009). Structures, Ionization Equilibria and Tautomerism of 6-Oxopurines in Solution. Journal of Physical Chemistry B, 113 (45):15101-1511.

    Namrata Jayanth, Srinivas Ramachandran and Mrinalini Puranik. (2009). Solution Structure of the DNA Damage Lesion 8-Oxoguanosine from Ultraviolet Resonance Raman Spectroscopy. Journal of Physical Chemistry A, 113 (8). 1459-1471.