D. Narasimha Rao



Indian Institute of Science, Bangalore, India. 1982

Postdoctoral Research

National Institutes of Health, U.S.A. 1983-1985
Dept. of Microbiology, Biozentrum University of Basel, Switzerland. 1986-1988
Dept. of Biochemistry, Cambridge University, England. 1988-1989
Tel: +91-80-22932538
Email: dnrao@biochem.iisc.ernet.in


  • DNA-Protein Interactions-using Restriction-Modification enzymes
  • DNA Mismatch Repair proteins as model systems.

The long term goal in the laboratory is to understand how DNA mismatch repair proteins and restriction -modification enzymes achieve their specificity.

  • ATP Dependent Restriction Enzymes
  • Many types of restriction enzymes cleave DNA away from their recognition site. Using type III restriction enzyme, EcoP15I, that cleaves DNA 25 - 27 bp away from its recognition site, we provide evidence to show that intact recognition site on cleaved DNA sequesters the restriction enzyme and decreases the effective concentration of the enzyme. EcoP15I restriction enzyme is shown here to perform only single round of DNA cleavage. More importantly, we show that an exonuclease activity is essential for EcoP15I restriction enzyme to perform multiple rounds of DNA cleavage, which might hold true for all restriction enzymes cleaving DNA sufficiently away from recognition site. Our results highlight the importance of functional cooperation in the modulation of enzyme activity. We are currently investigating the details of how these enzymes recognize, cleave and modify DNA , both from a biochemical and structural standpoint.

  • DNA Methyltransferases
  • With the availability of large quantities of N6-adenine methyltransferases (EcoP15I, EcoPI and KpnI) and a C5-cytosine methyltransferase (HhaI) we are interested in finding out how these enzymes recognize different sequences and carry out entirely different kinds of methylation reactions. Using steady-state kinetics and isotope-partioning experiments, the kinetic mechanisms of these methylases will be determined. We propose a detailed study of these enzymes using a variety of biochemical, biophysical and genetic approaches. These studies are thus aimed at understanding the precise interactions of the protein with DNA and to unravel the features of the enzyme action. It is hoped that these investigations would provide novel information on important molecular interactions.

  • DNA Mismatch Repair in Haemophilus influenzae
  • Haemophilus influenzae is a wide spread human pathogen, responsible for several primary and secondary infections leading to a variety of diseased conditions. Recent genetic studies have shown that the DNA mismatch repair genes of H. influenzae have a major role to play in its pathogenecity mediated through a phenomenon called phase variation. The present study is aimed at the biochemical characterization of several mismatch repair proteins and in understanding protein-protein interactions among the mismatch repair proteins of Haemophilus influenzae.

 Lab Members

 Key Publications

  • Madhusoodanan UK, Rao DN. (2010) Diversity of DNA methyltransferases that recognize asymmetric target sequences. Crit Rev Biochem Mol Biol. 45:125-45.
  • Kumar R, Mukhopadhyay AK, Rao DN. (2010) Characterization of an N6 adenine methyltransferase from Helicobacter pylori strain 26695 which methylates adjacent adenines on the same strand. FEBS J. 277:1666-1683.
  • Yadav VP, Mandal PK, Rao DN, Bhattacharya S. (2009) Characterization of the restriction enzyme-like endonuclease encoded by the Entamoeba histolytica non-long terminal repeat retrotransposon EhLINE1. FEBS J. 276:7070-82.
  • Duppatla V, Bodda C, Urbanke C, Friedhoff P, Rao DN. (2009) The C-terminal domain is sufficient for endonuclease activity of Neisseria gonorrhoeae MutL. Biochem J. 423:265-77.
  • Wootla B, Mahendra A, Dimitrov JD, Friboulet A, Borel-Derlon A, Rao DN, Uda T, Borg JY, Bayry J, Kaveri SV, Lacroix-Desmazes S. (2009) Factor VIII-hydrolyzing IgG in acquired and congenital hemophilia. FEBS Lett. 583: 2565-72.
  • Kranthi BV, Kumar R, Kumar NV, Rao DN, Rangarajan PN. (2009) Identification of key DNA elements involved in promoter recognition by Mxr1p, a master regulator of methanol utilization pathway in Pichia pastoris. Biochim Biophys Acta. 1789: 460-8.