Site-specific and general recombination are fundamental processes throughout nature. They are important in maintaining genetic diversity, regulation of expression, transposition, generation of the repertoire of antibodies, and the integration of viruses into the host chromosome. General recombination and double-stranded break repair are two ways of looking at the same event. It has become clear that human diseases, including some types of cancer, result from the failure to repair damage to DNA. This application focuses on the unique aspect of recombination of synapsis, the juxtaposition of like sequences on the surface of the recombinase. We will investigate the detailed structure of gamma/delta resolvase synaptic complex, the topology of synapsis by phage lambda integrative and excisive recombination, the stages in synapsis by the Escherichia coli RecA protein, and the mechanism of synapsis by yeast Sep1. The latter two are general recombination proteins, and the former are site-specific recombinases. We will investigate the means by which synapsis of the proper sequences is brought about in the face of a vast excess of competitor sequences. A critical aspect of synapsis inside a living cell is the effective concentration of DNA, a parameter that measures the net propensity of DNA to interact with other DNA or proteins. We will use the activity of recombinases in E. coli to study the effective concentration of DNA and to determine the factors that influence it.
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| Nollmann, Marcelo; Crisona, Nancy J; Arimondo, Paola B (2007) Thirty years of Escherichia coli DNA gyrase: from in vivo function to single-molecule mechanism. Biochimie 89:490-9 |
| Nollmann, Marcelo; Stone, Michael D; Bryant, Zev et al. (2007) Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque. Nat Struct Mol Biol 14:264-71 |
| Ptacin, Jerod L; Nollmann, Marcelo; Bustamante, Carlos et al. (2006) Identification of the FtsK sequence-recognition domain. Nat Struct Mol Biol 13:1023-5 |
| 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 |
| 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 |
| Breier, Adam M; Weier, Heinz-Ulrich G; Cozzarelli, Nicholas R (2005) Independence of replisomes in Escherichia coli chromosomal replication. Proc Natl Acad Sci U S A 102:3942-7 |
| Camara, Johanna E; Breier, Adam M; Brendler, Therese et al. (2005) Hda inactivation of DnaA is the predominant mechanism preventing hyperinitiation of Escherichia coli DNA replication. EMBO Rep 6:736-41 |
| Breier, Adam M; Cozzarelli, Nicholas R (2004) Linear ordering and dynamic segregation of the bacterial chromosome. Proc Natl Acad Sci U S A 101:9175-6 |
| Manna, Dipankar; Breier, Adam M; Higgins, N Patrick (2004) Microarray analysis of transposition targets in Escherichia coli: the impact of transcription. Proc Natl Acad Sci U S A 101:9780-5 |
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