Sankar Mitra, Ph.D.Dr. Mitra

Professor, Dept. of Biochemistry and Molecular Biology, Senior Scientist, Sealy Center for Molecular Medicine

Affiliations: Department of Biochemistry & Molecular Biology; Senior Scientist, Sealy Center for Molecular Science
Tel: (409) 772-1780
Fax: (409) 747-8608
samitra@utmb.edu

Research Interests

The broad research theme in the Mitra Laboratory is repair of oxidative damage in mammalian genomes and its signaling and regulation. The Mitra lab uses a comprehensive approach by utilizing a variety of tools ranging from enzymology, molecular/cellular biology to structural biology (in collaborative efforts) and transgenic mouse studies to address basic issues about mutagenesis/carcinogenesis, and aging caused by reactive oxygen species (ROS), which react with most cellular macromolecules, and are continuously generated during respiration. These are also induced exogenously due to inflammation, infection and anti-tumor drug treatment. Even though a variety of cellular processes have evolved to counter ROS, oxidative stress is required for many cellular signaling processes to maintain homeostasis. ROS are genotoxic, and generate a wide variety of mutagenic and toxic lesions in both nuclear and mitochondrial genomes, which are repaired primarily via the base excision repair (BER) pathway. Current research efforts in the Mitra Lab are focused on two topics, namely, (1) role of NEILs in repair of oxidatively damaged bases, and (2) distinct functions of APE1, a central player in base damage and single strand break repair with additional novel functions in transcription regulation.

Selected Publications

  1. Biswas, T., Clos II L. J., SantaLucia, J. Jr., Mitra, S., and Roy, R. Binding of Specific DNA Base Pair Mismatches by N-Methylpurine-DNA Glycosylase and its Implication in Initial Damage Recognition. J. Mol. Biol. 320:503-513, 2002.
  2. Bhakat, K. K., Izumi, T., Yang, S. H., Hazra, T. K. and Mitra, S. Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene, EMBO J. 22:6299-6309, 2003.
  3. Dou, H., Mitra, S. and Tapas K. Hazra, T. K. Repair of Oxidized Bases in DNA Bubble Structures by Human DNA Glycosylases NEIL1 and NEIL2. J. Biol. Chem. 278:49679-49684, 2003.
  4. Bhakat, K. K., Izumi, T., Yang, S. H., Hazra, T. K. and Mitra, S. Role of Acetylated Human AP-endonuclease (APE1/Ref-1) in Regulation of the Parathyroid Hormone Gene, EMBO J. 22:6299-6309, 2003.
  5. Szczesny, B., Hazra, T. K., Papaconstantinou, J., Mitra, S. and Boldogh, I. Age-dependent deficiency in import of mitochondrial DNA glycosylases required for repair of oxidatively damaged bases. PNAS 100:10670-10675, 2003. *(Special press release by PNAS.)
  6. Bhakat, K. B., Hazra, T. K. and Mitra, S. Acetylation of the Human DNA Glycosylase NEIL2 and Inhibition of Its Activity. Nucleic Acids Res. 32, 3033-3039, 2004.
  7. Mokkapati, S. K., Wiederhold, L., Hazra, T. K., and Mitra, S. Stimulation of DNA Glycosylase Activity of OGG1 by NEIL1: Functional Collaboration Between Two Human DNA Glycosylases. Biochemistry, 43:11596-11604, 2004.
  8. Wiederhold, L., Leppard, J. B., Kedar, P., Karimi-Busheri, F., Rasouli-Nia, A., Weinfeld, M., Tomkinson, A. E., Izumi, T., Prasad, R., Wilson, S. H., Mitra, S., and Hazra, T. K. AP Endonuclease-independent DNA Base Excision Repair in Human Cells. Molecular Cell 15, 209-220, 2004.
  9. Das, A., Rajagopalan, L., Mathura , V. S., Rigby, S. J., Mitra, S. and Hazra, T. K. Identification of a zinc finger domain in the human NEIL (Nei like)-2 protein. J. Biol. Chem. , 279 , 47132-47138, 2004.
  10. Das, A., Hazra, T. K., Boldogh, I., Mitra, S., and Bhakat, K. K. Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species. J. Biol. Chem. 280: 35272-35280 , 2005.
  11. Izumi, T., Brown, D. B., Naidu, C. V., Bhakat, K. K., MacInnes, M. A., Saito, H., Chen |, D. J. and Mitra, S. Two essential but distinct functions of the mammalian AP-endonuclease. Proc. Natl. Acad. Sci. 102:5739-5743, 2005.
  12. Bhakat, K. K., Mokkapati, S. K., Boldogh, I., Hazra, T. K., and Mitra, S. Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo. Mol. Cell. Biol.26:1654-1665 (2006).