Janice D. Pata, Ph.D.

Janice D. Pata, Ph.D.

Polymerases, Mutations, and the Evolution of Antimicrobial Drug Resistance
Director, Division of Scientific Cores
Associate Professor, Department of Biomedical Sciences, School of Public Health, University at Albany
B.S., California Institute of Technology
Ph.D., University of Colorado at Boulder
Postdoctoral training: Yale University
Fax: 518-402-4623

Research Interests

Genome replication is a fundamentally important process in all cells and viruses. Mistakes made during replication cause mutations as well as large scale genome rearrangements, which can ultimately cause antibiotic resistance in bacteria as well as aging, cancer and resistance to chemotherapy in humans. Cells contain multiple polymerases, yet our understanding of how all these enzymes contribute to genome stability is far from complete.

Of particular interest is how the DNA polymerases that are responsible for the majority of genome duplication are replaced by the more specialized polymerases that are responsible for translesion synthesis across from damaged DNA bases. While the translesion polymerases help cells tolerate DNA damage, they have a 10- to 1000-fold higher error rate than replicative polymerases and can substantially increase the frequency of mutations. The situation is made even more complex since most cells have multiple translesion polymerases, each with their own lesion-bypass and mutational specificities. Genome stability is thus critically dependent on which polymerase carries out DNA synthesis.

Our main research focus is on the replicative and translesion polymerases of Staphylococcus aureus, which is responsible for appoximately 300,000 antibiotic-resistant infections and 10,000 deaths every year in the United States. We characterize the relationships between the structure and biochemical activity of these polymerases using X-ray crystallography, pre-steady-state enzyme kinetics and site-directed mutagenesis and follow the evolution of antibiotic resistance in a model bioreactor system that recapitulates clinically relevant mutations identified in patients. Our goal is to identify new strategies for combating these infections.

We also have active collaborations with Dr. Alex Ciota to study the error-prone RNA genome replication of flaviviruses and with Drs. Kathleen McDonough and Haixin Sui to study transcriptional regulation in Mycobacterium tuberculosis.

Select Publications
Wu Y, Jaremko WJ, Wilson RC, Pata JD. Heterotrimeric PCNA increases the activity and fidelity of Dbh, a Y-family translesion DNA polymerase prone to creating single-base deletion mutations. DNA Repair. 2020; 96 102967. DOI: 10.1016/j.dnarep.2020.102967
Lasek-Nesselquist E, Lu J, Schneider R, Ma Z, Russo V, Mishra S, Pai MP, Pata JD, McDonough KA, Malik M. Insights into the evolution of Staphylococcus aureus daptomycin resistance from an in vitro bioreactor model. Frontiers in Microbiology. 2019; 10 345. DOI: 10.3389/fmicb.2019.00345
Ma Z, Lasek-Nesselquist E, Lu J, Schneider R, Shah R, Oliva G, Pata J, McDonough K, Pai MP, Rose WE, Sakoulas G, Malik M. Characterization of genetic changes associated with daptomycin nonsusceptibility in Staphylococcus aureus. PLoS One. 2018; 13 e0198366. DOI: 10.1371/journal.pone.0198366
Ranganathan S, Cheung J, Cassidy M, Ginter C, Pata JD, McDonough KA. Novel structural features drive DNA binding properties of Cmr, a CRP family protein in TB complex mycobacteria. Nucleic Acids Research. 2018; 46 403-420. DOI: 10.1093/nar/gkx1148
Griesemer SB, Kramer LD, Van Slyke GA, Pata JD, Gohara DW, Cameron CE, Ciota AT. Mutagen resistance and mutation restriction of St. Louis encephalitis virus. Journal of General Virology. 2017; 98 201-211. DOI: 10.1099/jgv.0.000682
Manjari SR, Pata JD, Banavali NK. Cytosine unstacking and strand slippage at an insertion-deletion mutation sequence in an overhang containing DNA duplex. Biochemistry. 2014; 53 (23): 3807–3816. DOI: 10.1021/bi500189g
Wilson RC, Jackson MA, Pata JD. Y-Family Polymerase Conformation Is a Major Determinant of Fidelity and Translesion Specificity. Structure. 2013; 21 (1): 20-31.
Mukherjee P, Lahiri I, Pata JD. Human polymerase kappa uses a template-slippage deletion mechanism, but can realign the slipped strands to favour base substitution mutations over deletions. Nucleic Acids Research. 2013; 41 (9): 5024-5035.
Lahiri I, Mukherjee P, Pata JD. Kinetic characterization of exonuclease-deficient Staphylococcus aureus PolC, a C-family replicative DNA polymerase. PLoS One. 2013; 8 (5): e63489.
Evans RJ, Davies DR, Bullard JM, Christensen J, Green LS, Guiles JW, Pata JD, Ribble WK, Janjic N, Jarvis TC. Structure of PolC reveals unique DNA binding and fidelity determinants. Proceedings of the National Academy of Sciences USA. 2008; 105 (52): 20695-700.
Wilson RC, Pata JD. Structural insights into the generation of single-base deletions by the Y family DNA polymerase dbh. Mol Cell. 2008; 29 (6): 767-79.
Full publication listing