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Chair and Professor of Biochemistry and Biophysics
Ph.D. Cornell University 1974

AIDS Research: 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.

Carcinogenesis: 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.

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.

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Recent Publications

Rossi ML, Pike JE, Wang W, Burgers PM, Campbell JL, Bambara RA (2008) Pif1 helicase directs eukaryotic Okazaki fragments toward the two-nuclease cleavage pathway for primer removal. J Biol Chem, 283:27483-93

Stewart JA, Miller AS, Campbell JL, Bambara RA (2008) Dynamic removal of replication protein A by Dna2 facilitates primer cleavage during Okazaki fragment processing in Saccharomyces cerevisiae. J Biol Chem, 283:31356-65

Li X, Nott SL, Huang Y, Hilf R, Bambara RA, Qiu X, Yakovlev A, Welle S, Muyan M (2008) Gene expression profiling reveals that the regulation of estrogen-responsive element-independent genes by 17beta-estradiol-estrogen receptor beta is uncoupled from the induction of phenotypic changes in cell models. J Mol Endocrinol, 40:211-29

Gehen SC, Staversky RJ, Bambara RA, Keng PC, O'Reilly MA (2008) hSMG-1 and ATM sequentially and independently regulate the G(1) checkpoint during oxidative stress. Oncogene,

Basu VP, Song M, Gao L, Rigby ST, Hanson MN, Bambara RA (2008) Strand transfer events during HIV-1 reverse transcription. Virus Res, 134:19-38

Song M, Basu VP, Hanson MN, Roques BP, Bambara RA (2008) Proximity and branch migration mechanisms in HIV-1 minus strand strong stop DNA transfer. J Biol Chem, 283:3141-50

Bartos JD, Willmott LJ, Binz SK, Wold MS, Bambara RA (2008) Catalysis of strand annealing by replication protein A derives from its strand melting properties. J Biol Chem, 283:21758-68

Jamburuthugoda VK, Santos-Velazquez JM, Skasko M, Operario DJ, Purohit V, Chugh P, Szymanski EA, Wedekind JE, Bambara RA, Kim B (2008) Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage. J Biol Chem, 283:9206-16

Gao L, Hanson MN, Balakrishnan M, Boyer PL, Roques BP, Hughes SH, Kim B, Bambara RA (2008) Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of Met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect. J Biol Chem, 283:9196-205

Gao L, Balakrishnan M, Roques BP, Bambara RA (2007) Insights into the multiple roles of pausing in HIV-1 reverse transcriptase-promoted strand transfers. J Biol Chem, 282:6222-31

Gehen SC, Vitiello PF, Bambara RA, Keng PC, O'Reilly MA (2007) Downregulation of PCNA potentiates p21-mediated growth inhibition in response to hyperoxia. Am J Physiol Lung Cell Mol Physiol, 292:L716-24

Purohit V, Roques BP, Kim B, Bambara RA (2007) Mechanisms that prevent template inactivation by HIV-1 reverse transcriptase RNase H cleavages. J Biol Chem, 282:12598-609

Rossi ML, Bambara RA (2006) Reconstituted Okazaki fragment processing indicates two pathways of primer removal. J Biol Chem, 281:26051-61

Bartos JD, Wang W, Pike JE, Bambara RA (2006) Mechanisms by which Bloom protein can disrupt recombination intermediates of Okazaki fragment maturation. J Biol Chem, 281:32227-39

Operario DJ, Balakrishnan M, Bambara RA, Kim B (2006) Reduced dNTP interaction of human immunodeficiency virus type 1 reverse transcriptase promotes strand transfer. J Biol Chem, 281:32113-21

Hanson MN, Balakrishnan M, Roques BP, Bambara RA (2006) Evidence that Creation of Invasion Sites Determines the Rate of Strand Transfer Mediated by HIV-1 Reverse Transcriptase. J Mol Biol, 363:878-90

Wang J, Dykes C, Domaoal RA, Koval CE, Bambara RA, Demeter LM (2006) The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. Virology, 348:462-74

Wang W, Lindsey-Boltz LA, Sancar A, Bambara RA (2006) Mechanism of stimulation of human DNA ligase I by the Rad9-rad1-Hus1 checkpoint complex. J Biol Chem, 281:20865-72

Rossi ML, Bambara RA (2006) Reconstituted okazaki fragment processing indicates two pathways of primer removal. J Biol Chem, 281:26051-61

Rossi ML, Purohit V, Brandt PD, Bambara RA (2006) Lagging strand replication proteins in genome stability and DNA repair. Chem Rev, 106:453-73

Stewart JA, Campbell JL, Bambara RA (2006) Flap endonuclease disengages Dna2 helicase/nuclease from Okazaki fragment flaps. J Biol Chem, 281:38565-72

Song M, Balakrishnan M, Chen Y, Roques BP, Bambara RA (2006) Stimulation of HIV-1 Minus Strand Strong Stop DNA Transfer by Genomic Sequences 3' of the Primer Binding Site. J Biol Chem, 281:24227-35

Operario DJ, Balakrishnan M, Bambara RA, Kim B (2006) Reduced dNTP interaction of human immunodeficiency virus type 1 reverse transcriptase promotes strand transfer. J Biol Chem, 281:32113-32121

Brandt PD, Helt CE, Keng PC, Bambara RA (2006) The Rad9 protein enhances survival and promotes DNA repair following exposure to ionizing radiation. Biochem Biophys Res Commun, 347:232-7

Domaoal RA, Bambara RA, Demeter LM (2006) HIV-1 reverse transcriptase mutants resistant to nonnucleoside reverse transcriptase inhibitors do not adversely affect DNA synthesis: pre-steady-state and steady-state kinetic studies. J Acquir Immune Defic Syndr, 42:405-11

Huang J, Li X, Qiao T, Bambara RA, Hilf R, Muyan M (2006) A tale of two estrogen receptors (ERs): how differential ER-estrogen responsive element interactions contribute to subtype-specific transcriptional responses. Nucl Recept Signal, 4:e015

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biochemistry
Ph.D. in Genetics
Ph.D. in Microbiology and Immunology

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: Robert_Bambara@urmc.rochester.edu

Robert Bambara
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 3-8553
Telephone: (585) 275-2764; Fax: (585) 275-6007