Base pair additions/deletions

The four types of mutagenic change are base-pair transformations, base-pair additions or deletions, large deletions and rearrangements, and unequal partition or nondisjunction. 

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. 

The addition or deletion of one or a few (but not 3) base pairs leads to a frameshift mutation. Large adducts, which are inside the double helix, can distort the DNA structure and are more likely to cause frameshift mutations. 

The best way to illustrate the importance of DNA repair is to consider the effects of unrepaired DNA damage (a lesion). The most serious outcome is a change in the base sequence of the DNA, which, if replicated and transmitted to future cell generations, becomes permanent. A permanent change in the nucleotide sequence of DNA is called a mutation. Mutations can involve the replacement of one base pair with another (substitution mutation) or the addition or deletion of one or more base pairs (insertion or deletion mutations). If the mutation affects nonessential DNA or if it has a negligible... 

Good evidence for the occurrence of the first type of mutation exists at least in bacteriophage of the T series, which infect Escherichia coli. The deletion or addition of a single base pair into a DNA chain of a gene should be expected to cause considerable difficulties in the translation of the code in the derived niRNA. into an amino acid sequence For example, if the mRNA of ihe nonmulant strain has the sequence ... 

The DNA alterations described above have involved covalent bonding of groups to nitrogenous bases. Another type of interaction is possible with highly planar (flat) molecules that are able to fit between base pairs (somewhat like slipping a sheet of paper between pages of a book), a phenomenon called intercalation. This can cause deletion or addition of base pairs, leading to mutation and cancer. A compound known to cause this phenomenon is 9-aminoacridine ... 

Recently, a quite different model has been proposed that accounts for the appearance of many kinds of mutations, including base pair substitutions, additions and deletions, and small chromosomal mutations of the type that would usually be classified as gene mutations. The model accounts for frequent palindromic sequences (more exactly, imperfect palindromes or quasipalindromes) in DNA that can predispose to alternative DNA structures (e.g., clover leaves) that differ from the usual double helix. The alternative or "secondary" structures can then be acted on by any of a variety of DNA-processing enzymes in ways that may ultimately lead to mutations. The details of these processes are only now becoming manifest, but the general model clearly explains many hitherto mysterious mutational phenomena.371... 

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. 

Molecular analysis of mtDNA from muscle biopsies often provides a definitive diagnosis of MELAS. Individuals with more severe clinical manifestations of MELAS generally have greater than 80% mutant mtDNA in postmitotic tissues such as muscle. In approximately 80% of MELAS cases, the responsible mutation is an A —> G base substitution at nucleotide position 3243. A smaller subset of MELAS patients (7.5%) possesses a different point mutation, aT C transition at nucleotide position 3271. At least eight additional point mutations and one four-base pair deletion mutation also have been described. 

The bacterial reverse mutation test (Ames Test) investigates the ability of chemicals and drags to induce reverse (back) mutations in bacteria, which involves base pair substitutions additions and/or deletions (frameshift mutations) of one or a few DNA base pairs. The bacterial strains used in the test system have mutations in genes coding for enzymes required for the biosynthesis of the amino acids histidine (Salmonella typhimurium) and tryptophan (Escherichia coli). If... 

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... 

Ames developed strains of bacteria that had carefully selected lethal mutations. In a test system the bacteria could survive only when its mutation had been corrected by experiencing another mutation caused by the tested material. This correction could be accomplished by causing a point mutation or frameshift mutations . Point mutations are base-pair substitutions, that is, a base change in DNA of at least one DNA base pair. In a reverse mutation test, this change in base pairs may occur at the site of the original mutation, or at a secondary site in the bacterial genome. Frameshift mutations are the addition or deletion of one or more base pairs in the DNA. Since amino acids are encoded by triplets of base pairs in sequence, any addition or deletion of 1 or 2 base pairs will dramatically alter the expressed protein from that point on. The Ames system employs strains of Salmonella typhimurium and Escherichia coli that require amino acids (histidine or tryptophan, respectively) to detect such reverse point and frameshift mutations. The reverse mutation allows the S. typhimurium or E. coli strains to restore the functional capability of the bacteria to be able to synthesize the specific amino acid on their own, independent of amino acid content in the medium. 

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