Genetic frameshifts

Genetic Make up of Tester Strains. The most widely used strains are those developed by Bruce Ames and colleagues which are mutant derivatives of the organism Salmonella typhimurium. Each strain carries one of a number of mutations in the operon coding for histidine biosynthesis. In each case the mutation can be reverted either by base-change or by frameshift mutations. The genotype of the commonly used strains is shown in Table 6.6. 

Streisinger, G., Okada, T., Emrich, J., Newton J., Tougita, A., Terzaghi, E. and Inouye, M. (1966). Frameshift mutations and the genetic code. Cold Spring Harbor Symp. Quantum Biol. 31 77-84. 

Mutations are often classified according to the effect they have on the structure of the gene s protein product. This change in protein structure can be predicted using the genetic code table in conjunction with the base sequence of DNA or mRNA. A variety of such mutations is listed in Table 1-4-1. Point mutations and frameshifts are illustrated in more detail in Figure 1-4-2. 

Vaisse, C., Qement, K., Guy-Grand, B., and Eroguel, P. (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20, 113-114. 

Lee SI, Umen JG, Varmus HE (1995) A genetic screen identifies cellular factors involved in retroviral-1 frameshifting. Proc Natl Acad Sci USA 92 6587-6591 Leeds P, Peltz SW, Jacobson A, Culbertson MR (1991) The product of the yeast UPFl gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Genes Dev 5 2303—... 

Frameshift mutations. Insertions or deletions of genetic material that lead to a shift in the translation of the reading frame. The mutation usually leads to nonfunctional proteins. 

Therefore, the genetic lesions caused by a mutagen can be detected in assays for many genetic end points, including base-pair substitution and frameshift mutation, deletion, mitotic recombination or gene conversion, unscheduled DNA synthesis, sister chromatid exchange, and chromosomal aberration.170... 

FRAMESHIFT MUTATION A gene mutation that occurs by the addition or deletion of one or a few base pairs and causes a shift in the reading frame of the genetic code, thereby altering the message encoded by all DNA base pairs that are read after the point of the mutation. 

Know the principles of the genetic code, the wobble hypothesis, and the concepts of nonsense, missense, and frameshift mutations and how they may be suppressed. 

Weiss R, Gallant J. Mechanism of ribosome frameshifting dnring 29. translation of the genetic code. Nature 1983 302 389-393. 

Fu C, Parker J. A rihosomal frameshifting error during translation of the argi mRNA of Escherichia coli. Mol. Gen. Genet. 38. 1994 243 434-441. 

Some of the tester strains are responsive to base-pair substitutions, whereas others detect deletions or additions of base pairs (frameshifts). The sensitivity of these specially designed strains has been enhanced by the genetic deletion of their excision-repair systems. Potential mutagens enter the tester strains easily because the lipopolysaccharide barrier that... 

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