Point mutation, reversion

Bacteria Mutation Salmonella typhimurium Salmonella/microsome test histidine reversions Point mutations reversion by base-pair substitution or frameshift mutation <3 wk L L L H... 

Yanofsky, C. and Crawford, I. P. (1959) The elfects of deletions, point mutations, reversions and suppressor mutations on the two components of the tryptophan synthetase of Escherichia coli. Proc. Nat. Acad. Sci. 45,1016-1026. 

M.M. Musa, N. Lott, M. Laivenieks, L. Watanabe, C. Vieille, R.S. Phillips, A single point mutation reverses the enantiopreference of Thermoarmerobacter ethanolicus secondary alcohol dehydrogenase, ChemCatChem 1 (2009) 89-93. 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

The test is commonly employed as an initial screen for genotoxic activity and, in particular, for point mutation-inducing activity. It detects point mutations, which involve substimtion, addition or deletion of one or a few DNA base pairs. The reverse mutation test in either Salmonella typhimurium or Escherichia coli detects mutation in an amino acid requiring strain (histidine or tryptophan, respectively) to produce a strain independent of an outside supply of amino acid. The principle of the test is that it detects mutations, which revert mutations present in the test strains and restore the functional capability of the bacteria to synthesize an essential amino acid. The revertant bacteria are detected by their ability to grow in the absence of the amino acid required by the parent test strain. 

Positive results from the bacterial reverse mutation test (often referred to as the Ames test) indicate that a substance induces point mutations by base pair substimtion or frameshift in the... 

Ecoflex (powder) was tested for its mutagenic potential on the basis of its ability to induce point mutations in several bacterial strains Salmonella typhimurium and Escherichia coll) in a reverse mutation assay (Ames test), according to OECD guideline 471. Results revealed that the polyester is not mutagenic to bacteria. 

Schatz O, Cromme FV, Gmninger-Leitch F, Le Grice SFJ. Point mutations in conserved amino acid residues within the C-terminal domain of HIV-1 reverse transcriptase specifically repress RNase H function. FEBS Lett 1989 257 311-314. 

Gardner, R.J., Bobrow, M., and Roberts, R.G., 1995, The identification of point mutations in Duchenne muscular dystrophy patients by using reverse-transcription PCR and the protein truncation test, Am J Hum Genet, 57, pp 311—320. 

Type IE vitamin D-dependent rickets is caused by a target tissue defect in response to l,25(OH)2D. Studies have shown a number of point mutations in the gene for the l,25(OH)2D receptor, which disrupt the functions of this receptor and lead to this syndrome. The serum levels of l,25(OH)2D are very high in type II but not in type I. Treatment with large doses of calcitriol has been claimed to be effective in restoring normocalcemia. Such patients are totally refractory to vitamin D. One recent report indicates a reversal of resistance to calcitriol when 24,25(OH)2D was given. These diseases are rare. 

Some dyes exhibit a mutagenic potential. The Ames test is commonly used as a first screening for the prediction of mutagenicity of a substance. It is a bacterial point mutation test inducing activity, which uses special strains of the bacteria Salmonella typhimurium with growth-dependence on the amino acid histidine. The dose-dependent reversion to histidine-independent growth is the marker for a point mutation. 

Mutation Escherichia coli WP2 tryptophan reversions Point mutations (base-pair substitutions) <3 wk L L M M... 

Fungi Mutation Saccharomyces cerevisiae Reversion of auxotrophic mutations (e.g. ilv in strain D7 several in strain XV185-14C) Point mutations <3 -wk L L S-M NA... 

Assays that detect reverse mutation are most popular, largely because of the development of the Salmonella/micro-some assay by Bruce Ames and his co-workers.10 13 All five of the strains that sure currently recommended95 contain point mutations that prevent the biosynthesis of histidine. Unless histidine is provided in the growth medium, the bacteria cannot grow. However, if a new mutation occurs at the site of the original mutation and "reverses" its effect, growth without histidine can take place. 

Single dose cynomolgus monkeys Repeat dose mice, rats, cynomolgus monkeys Fertility and early embryonic development rats Developmental rats, mice, rabbits Prenatal and postnatal development rats Genetic toxicology Ames reverse mutation, Chinese hamster ovary hypoxanthine guanine phosphoribosyl-transferase forward point mutation assay, cytogenetics in human lymphocytes... 

The bacterial reverse mutation test does not detect all compounds with the potential to induce point mutations. For some chemical series, modifications of the test system are necessary. For example, the potential for azo compounds to induce point mutations can only be detected by using an S9-mix prepared by hamster liver. To get an indication early in the development of a test compound for its potential to induce point mutations, modified test systems of the... 

In the point-mutation studies (1). Saccharomyces cerevisiae was used as the target cell, and the effects of the chemical were tested in a direct in vitro assay without metabolic activation and in a host-mediated modification. In the direct reverse-mutation assay, there were increases by a factor of 2-6 in the number of His revertants and by a factor of 2-7 in the number of trp revertants over the spontaneous frequencies. In contrast, there were no reported Increases in the number of Hls or trp revertants in the host-mediated assay. 

How likely is it to have a value matrix fV with pairs of conjugate complex eigenvalues Rumschitzki [8] showed that the value matrix JV can be converted to a symmetric matrix fV by means of a similarity transformation provided the corresponding mutation matrix Q is symmetric (Qij = Qji)-Then all eigenvalue of JV are real. Equal frequency of mutations in both directions, Ij - /j and 7j - Ij, is a realistic assumption unless the polynucleotide sequences under consideration contain so-called hot spots. These are positions at which point mutations are particularly frequent. It is unlikely that the reverse mutation leading to the sequence with the original hot spot is also an unusually frequent event. Therefore we expect a mutation matrix Q lacking symmetry in these cases. 

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