Transversion mutation

Single-base changes (point mutations) may be transitions or transversions. In the former, a given pyrimidine is changed to the other pyrimidine or a given... 

Figure 38-3. Diagrammatic representation of transition mutations and transversion mutations.

Figure 48-15. Simplified scheme of the causation of achondroplasia (MIM 100800). In most cases studied so far, the mutation has been a G to A transition at nucleotide 1138. In a few cases, the mutation was a G to C transversion at the same nucleotide. This particular nucleotide is a real "hot spot" for mutation. Both mutations result in replacement of a Gly residue by an Arg residue in the transmembrane segment of the receptor. A few cases involving replacement of Gly by Cys at codon 375 have also been reported.

Resistance to certain antibiotics can arise as a consequence of mutations to chromosomal genes because of changes in the DNA sequence. Mutations can occin due to single base pair changes. Transitions involve the substitution of one purine (A or G) for another and therefore one pyrimidine (C or T) for another. Transversions involve a change from a pyrimidine to a purine and vice versa. Frameshift mutations occin when one or... 

Mutations may be produced in many ways. Bases may be deleted or new ones may be inserted more frequently an existing base may be chemically modified so that on replication, improper base pairing will cause a different base to appear at the modified position. The latter type of mutation is called a replacement. When a purine is replaced by another purine or a pyrimidine by a different pyrimidine, the change is called a transition. A transversion is a change from pyrimidine to purine or purine to pyrimidine. 

In those cases where alkylation does not lead to depurination, it is more likely that the mutation will be of the transition type. However, when depurination does occur, on replication the position opposite the gap might be filled by any one of the four bases. This accounts for the transversions often caused by these agents. 

The base substitutions are primarily transversions at G C base pairs and the available evidence suggests that these mutations are induced by apurinic sites which are generated as secondary consequences of the initial alkylation event. The significance of these results in the context of carcinogenesis is briefly considered. 

BPDE reacts at several different sites on DNA to generate several kinds of lesions at the N2 (43-45) and N7 (46,47) positions of guanine, apurinic sites (48,49), and strand breaks (50). Which of these lesions are responsible for the transversion mutations at G C sites Evidence derived from a number of experiments suggests the hypothesis that apurinic sites generated by BPDE reactions with DNA are responsible for the transversion mutations ... 

The work of Loeb and Kunkel and their colleagues (70-72) has clearly established that apurinic sites in DNA are mutagenic they specifically cause transversion mutations, due to a strong preference for the incorporation of adenine residues during bypass of apurinic sites in template DNA. Thus, A T to T A and G C to T A transversions are the major mutagenic outcome generated by depurination of DNA. 

Both amber and ochre mutations can be generated at these sites, allowing both G C to T A and G C to C G transversions to be monitored. 

Point mutations can occur when one base is substituted for another (base substitution). Substitution of another purine for a purine base or of another pyrimidine for pyrimidine is called a transition, while substitutions of purine for pyrimidine or pyrimidine for purine are called transversions. Both types of base substitution have been identified within mutated genes. These changes lead to a codon change which can cause the wrong amino acid to be inserted into the relevant polypeptide and are known as mis-sense mutations. Such polypeptides may have dramatically altered properties if the new amino acid is close to the active center of an enzyme or affects the three-dimensional makeup of an enzyme or a structural protein. These changes, in turn, can lead to change or reduction in function, which can be detected as a change in phenotype of the affected cells. 

A transversion is a point mutation that replaces a purine-pyrimidine base pair with a pyriinidine-purine base pair. For example, an A-T base pair becomes a T-A or a C-G base pair. 

Point mutations or single base substitutions are classified as transitions or transversions. 

The base substitutions can be either a change from one purine or pyrimidine to another, which is a transition or a change of a purine for a pyrimidine and vice versa, which is a transversion. A chemical change in the base or formation of an adduct, which changes the nature of the base(s), could cause a substitution at replication. The position of the adduct on the particular DNA base would determine the type of mutation. 

Mutations in the coding sequences, which will include genes for specific proteins, will potentially cause adverse changes in the gene and therefore the phenotype. Chemicals can interact with DNA in a variety of ways including adduct formation, base substitutions (transitions or transversions), and base additions or deletions. 

Both NER and BER forms of excision repair remove a great variety of defects, many of which are a result of oxidative damage.657 720 Most prominent among these is 7,8-dihydro-8-oxoguanine (8-OG), which is able to base pair with either cytosine (with normal Watson-Crick hydrogen bonding) or with adenine, which will yield a purine-purine mismatch and aC G —> A T transversion mutation (Eq. 27-24), a frequent mutation in human cancers.721 722... 

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