Transcript Slippage and Recoding
Accurate transmission of genetic information during transcription requires that RNA polymerases maintain the correct register of the active site during each cycle of nucleotide incorporation. The RNA:DNA hybrid plays an important role in maintaining this lateral stability, and it has been observed that when the polymerase encounters homopolymeric tracts in the DNA template the transcript and/or the transcription complex may slip along the template, allowing the polymerase to incorporate more or fewer nucleotides than are encoded by the template. This phenomenon has been observed during all phases in the transcription cycle, including initiation, elongation, and termination. Here we review the evidence for transcript slippage in vivo and its implications for miscoding events. In addition, we review experiments that bear upon the mechanistic aspects of transcript slippage and the parameters that may affect its frequency. Aside from its implications for miscoding, transcript slippage may also be involved in regulatory roles during initiation and termination and promote expression of alternative information from the same gene.
KeywordsElongation Complex Nucleotide Incorporation Homopolymeric Tract Brownian Ratchet Transcription Bubble
These studies were supported by grants from the National Institutes of Health (GM38147) and from the Foundation of UMDNJ to WTM. We are grateful to Chuck Turnbough, Don Luse, Sergei Borukhov, Dimitriy Markov, Steven Emanuel, and Maria Savkina for helpful comments, and to Mr. Raymond Castagna for technical support. We thank Craig Martin for pointing out to us the special properties of An:Tn homoduplexes that might provide a basis for transcript slippage, and Irina Artsimovitch and Evgeny Nudler for the gift of EcoRIQ111A.
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