The integrity of the genetic information encoded by DNA is essential to the survival of all organisms. However, the chemically reactive bases of DNA are continuously subjected to modifications arising from normal cellular metabolism and from exogenous sources. Thus, a variety of  alkylation, deamination and oxidation events produce perhaps thousands of cytotoxic and mutagenic base per cell per day, which can lead to cancer and other diseases. To counteract this inevitable damage, the cellular machinery includes DNA repair systems. The repair of damage involving a single base typically proceeds via the base excision repair (BER) pathway, initiated by a damage-specific DNA glycosylase. Human thymine DNA glycosylase  (hTDG) is a key DNA glycosylase in the base excision repair (BER) pathway which removes T from G•T mispairs, producing an abasic (or AP) site, to which it binds tightly. Follow-on base excision repair proteins displace hTDG, excise the AP nucleotide, and restore the G•C pair. hTDG is inactive against the huge excess of normal A•T pairs, and is most effective for G•T mispairs and other lesions located within a CpG site. The long term goal of our research is to understand the mechanism by which the enzyme recognize and excise the damaged bases, yet exclude normal base, which may help in better understanding of cancer, aging and genetic diseases.

We use X-ray crystallography, NMR spectroscopy and variety of other biophysical, biochemical and molecular biological techniques to evaluate the structure and mechanism of the hTDG.

B.Sc. in Chemistry, University of Calcutta, West Bengal, India. (1996)

M.Sc. in Organic Chemistry, University of Calcutta, West Bengal, India. (1998)

Ph.D. in Bio-organic & Bio-physical chemistry , Bose Institute, Kolkata, West Bengal, India. (2006)

Postdoctoral Fellow, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD. (2006 - present.)

Atanu Maiti, Michael T. Morgan and Alexender C. Drohat, Role of two strictly conserved residues in nucleotide flipping and N-glycosylic bond cleavage by human Thymine DNA glycosylase, J Biol Chem, 2009, Oct 30.

 

Atanu Maiti, Michael T. Morgan, Edwin Pozharski and Alexender C. Drohat, Crystal structure of human thymine DNA glycosylase bound to DNA elucidates sequence-specific  mismatch recognition, Proc Natl Acad Sci, 2008, Vol. 105, no. 26, 8890-8895

 

Atanu Maiti and Siddhartha Roy, Switching DNA-binding specificity by unnatural amino acid substitution, Nucleic Acid research,2005, Vol. 33, No. 18, 5896-5903.