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Robert Bambara is a Professor of Biochemistry and Biophysics at the University of Rochester. Dr. Bambara's lab examines DNA replication and expression. In the molecular mechanism of recombination, HIV evades immune response and drug therapy by rapidly evolving its structure. One source of rapid viral genome evolution is recombination between viral genomes at hot spots on RNA strands that are being copied. We recently found that sites on the genomes with particular RNA hairpin structure can engage in an RNA/RNA interaction called "kissing," which facilitates the crossover process of recombination. Remarkably we can use this knowledge and the results of experiments in vitro, to accurately predict recombination during infections. Future work involves determining all of the protein and RNA structural factors that promote recombination, and how this knowledge can be used for effective HIV therapy.
The lab's work also includes carcinogenesis and the mechanisms of DNA repair and replication. When mammalian chromosomal DNA is damaged, a mechanism is employed to stop DNA replication until the damage is repaired. This prevents a proliferation of errors in sequence that cause aging and cancer. Recent cloning and expression of a number of key DNA replication and repair proteins allow us to reconstitute this process. Interestingly, it works by having many of the same proteins that normally carry out replication, shift to a repair mode. An understanding of this regulation, could be used to delay carcinogenesis and to make forms of chemotherapy more effective.
Another area of focus is steroid responsive elements and hormone receptors. Steroid hormone receptor proteins regulate genes for growth and development of cells. They also can respond to hormones in a way that promotes growth of tumors. The estrogen receptor responds to estradiol for natural growth regulation by binding a specific DNA sequence element near the promoter of a responsive gene. It then binds transcriptional regulatory proteins that can activate the promoter. Antiestrogens are effective suppressors of breast tumors because they interfere with this process. How they alter receptor binding to DNA and activation of the promoter is the subject of our research. | 