The major focus of the work will be on the application of topological and genetic approaches to the study of several key enzymes in DNA metabolism. This will involve developing new techniques for determining DNA structure and expanding the theory of DNA folding. In addition, we hope to isolate mutants of E. coli topoisomerase III to determine its function in vivo. We will also investigate the enzymes in E. coli that metabolize DNA knots and catenases and measure the functional level of DNA supercoiling in this organism and perhaps in yeast. Using a rigorous topological method, the mechanism of chromosome segregation in several organisms will be tested. Analogous methods will be brought to bear on the mechanism of topoisomerases. We will continue our studies of transcription by RNA polymerase III and its accessory factors. This will involve purification of the factors and determination of their role, analysis of the formation of transcription complexes, measurement of the DNA binding sites, and exploration of the striking increase in a polymerase III transcript after neoplastic transformation.
| Cost, Gregory J; Cozzarelli, Nicholas R (2007) Directed assembly of DNA molecules via simultaneous ligation and digestion. Biotechniques 42:84, 86-9 |
| Cost, Gregory J; Cozzarelli, Nicholas R (2006) Smc5p promotes faithful chromosome transmission and DNA repair in Saccharomyces cerevisiae. Genetics 172:2185-200 |
| Gore, Jeff; Bryant, Zev; Stone, Michael D et al. (2006) Mechanochemical analysis of DNA gyrase using rotor bead tracking. Nature 439:100-4 |
| Stray, James E; Crisona, Nancy J; Belotserkovskii, Boris P et al. (2005) The Saccharomyces cerevisiae Smc2/4 condensin compacts DNA into (+) chiral structures without net supercoiling. J Biol Chem 280:34723-34 |
| Pease, Paul J; Levy, Oren; Cost, Gregory J et al. (2005) Sequence-directed DNA translocation by purified FtsK. Science 307:586-90 |
| Levy, Oren; Ptacin, Jerod L; Pease, Paul J et al. (2005) Identification of oligonucleotide sequences that direct the movement of the Escherichia coli FtsK translocase. Proc Natl Acad Sci U S A 102:17618-23 |
| Hardy, Christine D; Cozzarelli, Nicholas R (2003) Alteration of Escherichia coli topoisomerase IV to novobiocin resistance. Antimicrob Agents Chemother 47:941-7 |
| Khodursky, Arkady B; Bernstein, Jonathan A; Peter, Brian J et al. (2003) Escherichia coli spotted double-strand DNA microarrays: RNA extraction, labeling, hybridization, quality control, and data management. Methods Mol Biol 224:61-78 |
| VanLoock, Margaret S; Alexandrov, Alexander; Yu, Xiong et al. (2002) SV40 large T antigen hexamer structure: domain organization and DNA-induced conformational changes. Curr Biol 12:472-6 |
| Dekker, N H; Rybenkov, V V; Duguet, M et al. (2002) The mechanism of type IA topoisomerases. Proc Natl Acad Sci U S A 99:12126-31 |
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