Investigators and Program Directors

Research Interests

The work in the lab is aimed at understanding the macromolecular machines that replicate cellular and viral genomes. We study the structures and activities of several important polymerases with specialized functions, using the tools of X-ray crystallography, biochemistry and molecular biology. The classes of polymerases currently under investigation are:

Lesion-bypass DNA polymerases. The Y-family of lesion-bypass DNA polymerases can synthesize DNA opposite damaged template bases. They can replace replicative DNA polymerases that stall at lesion sites, allowing DNA replication to continue. Several subfamilies of these polymerases exist, with each displaying specificity for a unique set of lesions. The polymerase eta subfamily, for example, bypasses thymidine dimers and acts as a tumor suppressor in humans. The DinB subfamily can bypass benzpyrene adducts of DNA, a byproduct of tobacco smoke, and the human version of the enzyme is over-expressed in lung cell cancers. We want to understand, at the molecular level, the specificity of lesion-bypass and how the different DNA polymerases in a cell are all coordinated so that replication is accurate and complete.

Reverse transcriptases. Retroviral reverse transcriptases are responsible for generating a double-stranded DNA copy of the viral RNA genome. This is a complex process that requires DNA polymerase and RNase H activities, as well as two specific initiation events and two template-switching events. The reverse transcriptase of HIV-1 is a major target of anti-retroviral drug therapies. However, the enzyme can rapidly acquire mutations that render it resistant to these treatments. By understanding the molecular details of the replication process we may be able to design improved reverse transcriptase inhibitors.

Cellular RNA-directed RNA polymerases. Until recently, RNA-directed RNA polymerases, which make an RNA copy of an RNA template without any DNA intermediate, were thought to be encoded only by RNA viruses. Cellular enzymes with this activity have been identified within the last few years and are involved in the process of RNA interference. This process appears to have evolved, at least in part, as a cellular anti-viral defense mechanism. We aim to investigate the polymerases in this new family by characterizing their enzymatic properties and by determining their structural relationship to other polymerase families.

Contact Information

Office: 518-402-2595
Lab: 518-402-4673
FAX: 518-402-4623
Email: jpata@wadsworth.org

Mailing address:
Wadsworth Center
New York State Department of Health
P.O. Box 509
Albany, NY 12201-0509

Street address:
Center for Medical Sciences
150 New Scotland Avenue
Albany, NY 12208