Homologous genetic recombination is the molecular basis for genetic exchanges upon which much of the science of genetics is based. The success of future trials in human gene therapy is also likely to depend upon our understanding of the cellular systems promoting recombination. In bacteria, the primary function of homologous genetic recombination is recombinational DNA repair. When a replication fork is halted at DNA damage, a complex system of enzymatic functions effects repair and reinitiates DNA replication. The bacterial RecA protein promotes the central steps in this process, including DNA pairing and strand exchange. Homologs of RecA protein are found in all organisms, with Rad51 protein being the best-studied eukaryotic protein in this class. The major goal of this grant is to provide a detailed understanding of the DNA strand exchange reaction promoted by RecA protein in vitro. The proposal is focused on four initiatives. The first is directed at a better understanding of the end-dependent assembly and disassembly of RecA filaments on DNA. Second the mechanism by which two DNAs are first aligned in recombination will be studied, including tests of a proposed triplex DNA pairing intermediate. Third, the activities of other DNA strand exchange proteins including other bacterial RecA proteins and the RadA protein of E. coli will be studied. An examination of these protein will help to define the range of activities that occur in this class of proteins to better relate in vitro activities to in vivo function and help test models for DNA strand exchange.
| 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 |
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| 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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