The RecA protein of E. coli promotes a DNA strand exchange reaction in vitro that provides a convenient molecular model for the central steps of homologous genetic recombination. This protein is the prototype for a family of recombinases found in all organisms. In humans, the primary RecA homologue (hRad51) is part of a major pathway for tumor suppression. The long-range goal of the research in this proposal is a detailed understanding of the regulation and function of RecA protein. The hypothesis that recombinational DNA repair of stalled replication forks is the primary function of RecA protein provides an intellectual framework. The project has evolved to include the RecA proteins of E. coli and D. radiodurans, as well as the Rad51 protein of yeast. There are four major areas of emphasis: (a) structure-function relationships, (b) general biochemistry of RecA family recombinases, (c) regulation of RecA, and (d) special functions of RecA protein. Structure-function efforts are focused on two initiatives. First, we are examining a number of mutant RecA proteins in which the coupling of ATP hydrolysis to one or more functions is disrupted. We also have several projects to elucidate the structure of RecA protein bound to DNA. Biochemical studies are focused on recombinase filament assembly and disassembly, DNA pairing and strand exchange, and the role of ATP hydrolysis in recombinase reactions. The work on the regulation of RecA protein includes efforts to investigate the function of the RecFOR, RecX, Dinl, RecL, RdgC, UvrD, and PsiAB proteins. Special functions of RecA under investigation include the RecA-stimulated translesion DNA synthesis reaction of DNA polymerase V, and may be extended to include a new effort to understand DNA crosslink repair.
| Stanage, Tyler H; Page, Asher N; Cox, Michael M (2017) DNA flap creation by the RarA/MgsA protein of Escherichia coli. Nucleic Acids Res 45:2724-2735 |
| Lewis, Jacob S; Spenkelink, Lisanne M; Jergic, Slobodan et al. (2017) Single-molecule visualization of fast polymerase turnover in the bacterial replisome. Elife 6: |
| Chen, Stefanie H; Byrne-Nash, Rose T; Cox, Michael M (2016) Escherichia coli RadD Protein Functionally Interacts with the Single-stranded DNA-binding Protein. J Biol Chem 291:20779-86 |
| Bakhlanova, Irina V; Dudkina, Alexandra V; Wood, Elizabeth A et al. (2016) DNA Metabolism in Balance: Rapid Loss of a RecA-Based Hyperrec Phenotype. PLoS One 11:e0154137 |
| Jaszczur, Malgorzata; Bertram, Jeffrey G; Robinson, Andrew et al. (2016) Mutations for Worse or Better: Low-Fidelity DNA Synthesis by SOS DNA Polymerase V Is a Tightly Regulated Double-Edged Sword. Biochemistry 55:2309-18 |
| Ronayne, Erin A; Wan, Y C Serena; Boudreau, Beth A et al. (2016) P1 Ref Endonuclease: A Molecular Mechanism for Phage-Enhanced Antibiotic Lethality. PLoS Genet 12:e1005797 |
| Leite, Wellington C; Galvão, Carolina W; Saab, Sérgio C et al. (2016) Structural and Functional Studies of H. seropedicae RecA Protein - Insights into the Polymerization of RecA Protein as Nucleoprotein Filament. PLoS One 11:e0159871 |
| Gruber, Angela J; Olsen, Tayla M; Dvorak, Rachel H et al. (2015) Function of the N-terminal segment of the RecA-dependent nuclease Ref. Nucleic Acids Res 43:1795-803 |
| Robinson, Andrew; McDonald, John P; Caldas, Victor E A et al. (2015) Regulation of Mutagenic DNA Polymerase V Activation in Space and Time. PLoS Genet 11:e1005482 |
| Kim, Taejin; Chitteni-Pattu, Sindhu; Cox, Benjamin L et al. (2015) Directed Evolution of RecA Variants with Enhanced Capacity for Conjugational Recombination. PLoS Genet 11:e1005278 |
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