Slippery Runs, Shifty Stops, Backward Steps, and Forward Hops: -2, -1, +1, +2, +5, and +6 Ribosomal Frameshifting

Abstract

Frameshift mutations frequently express residual levels of gene activity; that is, they are often leaky. This leakiness can be used as a tool to define the functional components that affect the reading frame during gene expression (Atkins et al. 1972; Fox and Weiss-Brummer 1980; Weiss and Gallant 1983). Recent technological advances in the capability to efficiently build synthetic DNA sequences have facilitated the construction of small, defined "frameshift windows." These windows are regions where frameshift events can be detected and measured. The cloned synthetic window is fused onto the 5′ coding region of an active β-galactosidase gene that provides a sensitive monitor for the frameshift events. Fusions onto the lacZ gene have the advantages of simple colorimetric assays for β-galactosidase activity and little or no effect of the fused sequence on the specific activity or stability of the enzyme (Miller and Albertini 1983). A frameshift event also leaves a clue...