Anne Grove
Anne Grove
agrove@lsu.edu
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We are interested in protein-nucleic acid interactions, with a particular emphasis on proteins that bend and supercoil DNA. The classical “architectural proteins”, so named because their primary function is to alter the conformation of the DNA duplex, include the eukaryotic High Mobility Group (HMGB) proteins and the bacterial histone-like HU proteins, essential in maintaining the integrity of eukaryotic chromatin and the bacterial nucleoid, respectively. Architectural DNA-binding proteins also play important roles in processes such as DNA recombination and transcription due to their role in mediating the assembly of larger nucleoprotein complexes.
We are focusing on the yeast HMGB proteins HMO1/2, which more closely resemble vertebrate HMGB proteins by having two HMG-boxes. We have demonstrated the contribution of each protein domain of HMO1 to DNA binding, and we are currently focusing on defining in vivo roles. Another project concerns bacterial nucleoid-associated proteins. We have specified the molecular basis for substrate specificity in HU proteins, with a current focus on the unusual properties of mycobacterial HU homologs. The unusually radiation-resistant eubacterium Deinococcus radiodurans encodes an HU homolog with preferred binding to four-way DNA junctions; we are presently analyzing the role of D. radiodurans HU in recombination, as well as other D. radiodurans-encoded proteins with potential roles in prevention of oxidative DNA damage.
Type IB topoisomerases are found in eukaryotes and in a small subset of eubacteria. We are focusing on defining the interaction between fluoroquinolone antibiotics and topoisomerase I from the poxvirus Vaccinia. We are also characterizing a homolog from the eubacterium Pseudomonas aeruginosa. The significance of developing potent inhibitors of these two enzymes relates to the potential use of the closely related smallpox virus as a biological weapon and to the frequently lethal nosocomial infections caused by P. aeruginosa, respectively.
Bhattacharyya, G. and Grove, A. The N-terminal extensions of Deinococcus radiodurans Dps-1 mediate DNA major groove interactions as well as assembly of the dodecamer. J. Biol. Chem. 282, 11921-11930 (2007).
Tsihlis, N. D. and Grove, A. The Saccharomyces cerevisiae RNA polymerase III recruitment factor subunits Brf1 and Bdp1 impose a strict sequence preference for the downstream half of the TATA box. Nucleic Acids Res. 34, 5585-5593 (2006).
Bauerle, K. T., Kamau, E. and Grove, A. Interactions between the N- and C-terminal domains of the Saccharomyces cerevisiae high mobility group protein HMO1 are required for DNA bending. Biochemistry 45, 3635-3645 (2006).
Ghosh, S. and Grove, A. The Deinococcus radiodurans-encoded HU protein has two DNA-binding domains. Biochemistry 45, 1723-1733 (2006).
Wilkinson, S. P. and Grove, A. Negative cooperativity of uric acid binding to the transcriptional regulator HucR from Deinococcus radiodurans. J. Mol. Biol. 350, 617-630 (2005).
Grove, A. and Wilkinson, S. P. Differential DNA binding and protection by dimeric and dodecameric forms of the ferritin homolog Dps from Deinococcus radiodurans. J. Mol. Biol. 347, 495-508 (2005).
Kamau, E., Bauerle, K. T. and Grove, A. The Saccharomyces cerevisiae High Mobility Group Box protein HMO1 contains two functional DNA-binding domains. J. Biol. Chem. 279, 55234-55240 (2004).
Wilkinson, S. P. and Grove, A. HucR, a novel uric acid responsive member of the MarR family of transcriptional regulators from Deinococcus radiodurans. J. Biol. Chem. 279, 51442-51450 (2004).
