The Accuracy of Molecular Processes
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Recombination is arguably one of the most fundamental mechanisms driving genetic diversity during evolution. Recombination takes place in one way or another from viruses such as HIV and polio, to bacteria, and finally to man. In both prokaryotes and eukaryotes, homologous recombination is assisted by enzymes, recombinases, that promote the exchange of strands between two segments of DNA, thereby creating new genetic combinations. In bacteria, homologous recombination takes place as a pathway for the repair of DNA lesions and also during horizontal or lateral gene transfer processes, in which cells take in exogenous pieces of DNA. This allows bacteria to evolve rapidly by acquiring large sequences of DNA, a process which would take too long by gene duplications and single mutations. I will survey recent results on the fidelity of homologous recombination as catalyzed by the bacterial recombinase RecA. These results show discrimination up to the level of single base mismatches, during the initial stages of the recombination process. A cascaded kinetic proofreading process is proposed to explain this high discrimination. Kinetic proofreading ideas are also reviewed.
KeywordsHomologous recombination DNA RecA FRET
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- 3.Morel, P., Stasiak, A., Ehrlich, S.D. and Cassuto, E. (1994) Effect of length and location of heterologous sequences on RecA-mediated strand exchange. J. Biol. Chem., 269, 19830–19835.Google Scholar
- 5.Feng, G., Tsui, H.C.T. and Winkler, M.E. (1996) Depletion of the cellular amounts of the MutS and MutH methyl-directed mismatch repair proteins in stationary-phase Escherichia coli K-12 cells. J. Bacterial., 178, 2388–2396.Google Scholar
- 11.Majewski, J. and Cohan, F.M. (1999) DNA sequence similarity requirements for interspecific recombination in bacillus. Genetics, 153, 1525–1533.Google Scholar
- 12.Shen, R and Huang, H.V. (1986) Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics, 112, 441–457.Google Scholar