Satya Prakash , Ph.D.

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

6.104 Blocker Medical Research Building
Galveston, TX 77555-1061 USA
Telephone: 409-747-8602
Fax: 409-747-8608
e-mail: s.prakash@utmb.edu

Our research focuses on deciphering mechanisms of translesion DNA synthesis in eukaryotes. DNA polymerase η was discovered in our laboratory, and its role in the error-free bypass of cyclobutane pyrimidine dimers and in the bypass of many other distorting DNA lesions has been established from studies done in our group. Its biological relevance was revealed from the observation that its mutational inactivation causes the cancer prone syndrome, the variant form of xeroderma pigmentosum in humans.

In addition to Polη, human cells contain a number of other DNA polymerases able to replicate through DNA lesions. Biochemical studies done in our group and structural studies done in collaboration with Aneel Aggarwal's group at Mt. Sinai School of Medicine, NY, have led us to conclude that these various polymerases are highly specialized for their roles in lesion bypass; moreover, their mechanisms for replicating DNA are fundamentally different from classical replicative DNA polymerases. For example, DNA polymerase ι uses Hoogsteen base pairing instead of the normal Watson-Crick base pairing for DNA synthesis, and in Rev1, another DNA polymerase with a specialized role in lesion bypass, the templating base is evicted from the DNA helix and the incoming nucleotide pairs with an arginine residue of Rev1. Such a DNA synthesis mode enables Rev1 to efficiently carry out nucleotide insertion opposite a large array of DNA adducts that severely impinge upon the minor groove.

In addition to establishing new paradigms for polymerase action and elucidating the translesion synthesis mechanisms for yeast and human cells, our more recent ongoing studies in yeast are yielding insights into the mechanisms of lesion bypass processes other than translesion DNA synthesis, and they are beginning to unravel the interconnections that ensure the coordination of replication fork progression with the various lesion bypass processes and with the cell cycle checkpoint machinery.

Selected Publications

  1. Nair, D. T., R. E. Johnson, S. Prakash, L. Prakash, and A. K. Aggarwal (2004) Replication by human DNA polymerase-ι occurs by Hoogsteen base-pairing. Nature 430: 377-380.
  2. Uljon, S. N., R. E. Johnson, T. A. Edwards, S. Prakash, L. Prakash, and A. K. Aggarwal (2004) Crystal structure of the catalytic core of human DNA polymerase kappa. Structure 12: 1395-1404.
  3. Prakash, S., R. E. Johnson, and L. Prakash (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu. Rev. Biochem. 74:317-353.
  4. Wolfle, W.T, M. T. Washington, E. T. Kool, T. E. Spratt, S. A. Helquist, L. Prakash, and S. Prakash (2005) Evidence for a Watson-Crick hydrogen bonding requirement in DNA synthesis by human DNA polymerase κ. Mol. Cell. Biol. 25: 7137-7143.
  5. Nair, D. T., R. E. Johnson, L. Prakash, S. Prakash, and A. K. Aggarwal (2005) Rev1 employs a novel mechanism of DNA synthesis using a protein template. Science 309: 2219-2222.
  6. Haracska, L., R. E. Johnson, L. Prakash, and S. Prakash (2005) Trf4 and Trf5 proteins of Saccharomyces cerevisiae exhibit poly(A) RNA polymerase activity but no DNA polymerase activity. Mol. Cell. Biol. 25: 10183-10189.
  7. Guzder, S. N., C. H. Sommers, L. Prakash, and S. Prakash (2006) Complex formation with damage recognition protein Rad14 is essential for Saccharomyces cerevisiae Rad1-Rad10 nuclease to perform its function in nucleotide excision repair in vivo. Mol. Cell. Biol. 26: 1135-1141.
  8. Ribar, B., L. Prakash, and S. Prakash (2006) Requirement of ELC1 for RNA polyubiquitylation and degradation in response to DNA damage in Saccharomyces cerevisiae. Mol. Cell. Biol.26: 3999-4005.
  9. Johnson, R. E., L. Haracska, L. Prakash, and S. Prakash (2006) Role of Hoogsteen edge hydrogen bonding at template purines in nucleotide incorporation by human DNA polymerase Ι. Mol. Cell. Biol. 26: 6435-6441.
  10. Johnson, R.E., L. Prakash, and S. Prakash (2006) Yeast and human translesion DNA synthesis polymerases: expression, purification, and biochemical characterization. Methods in Enzymology, 408: 390-407.