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Satya Prakash, PhD

Professor, Department of Biochemistry & Molecular Biology,
Sealy Center for Molecular Medicine

Phone: (409) 747-8602

Satya Prakash, PhD

Research Summary

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. Silverstein, T. D., R. E. Johnson, R. Jain, L. Prakash, S. Prakash, and A. K. Aggarwal (2010) Structural basis for the suppression of skin cancers by DNA polymerase eta. Nature 465: 1039-1043.

  2. Silverstein, T. D., R. Jain, R. E. Johnson, L. Prakash, S. Prakash, and A. K. Aggarwal (2010) Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase h.  Structure 18: 1463-1470.

  3. Johnson RE, Prakash L, Prakash S. Pol31 and Pol32 subunits of yeast DNA polymerase d are also essential subunits of DNA polymerase z. Proc. Natl. Acad. Sci. 2012:109(31):12455-12460.

  4. Jain R, Vanamee, ES, Dzikovski BG, Buku A, Johnson RE, Prakash L, Prakash S, Aggarwal AK. An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase e. J. Mol. Biol. 2014:426:301-308.

  5. Johnson, R. E., Klassen, R., Prakash, L. Prakash, S. A major role of DNA polymerase d in replication of both the leading and lagging DNA strands.  Mol. Cell 2015: 59:163-175.

  6. Conde, J., Yoon, J-H, Roy Choudhury, J., Prakash, L., Prakash S.  Genetic control of replication through N1-methyladenine in human cells.  J. Biol. Chem. 2015: 290:29794-29800.

  7. Yoon,J.-H., Park, J., Conde, J., Wakamiya, M., Prakash, L. Prakash, S. Rev1 promotes replication through UV lesions in conjunction with DNA polymerases h, i, and k but not DNA polymerase z. 2015 Genes & Dev. 29:2588-2602.

  8. Coloma, J., Johnson, R.E., Prakash, L., Prakash, S., Aggarwal, A.K.  Human DNA polymerase a in binary complex with a DNA:DNA template-primer.  Scientific Reports 2016: Apr 1;6:23784. doi: 10.1038/srep23784

  9. Rechkoblit, O., Gupta, Y. K., Malik, R., Rajashankar, R., Johnson, R. E., Prakash, L., Prakash, S., and Aggarwal, A. K. Structure and mechanism of human PrimPol, a DNA polymerase with primase activity.  Science  Advances 2016: 2:e1601317

  10. Jain, R., Choudhury, J. R., Buku, A., Johnson, R. E., Prakash, L., Prakash, S. and Aggarwal, A. K. Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-i.  Sci. Rep. 2017  Mar 8; 7, 43904; doi: 10.1038/srep4309.