Insertions replication mutations

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. 

Many of the mutations caused by artificially produced base analogues are transitions. Mutations are produced by base analogues in one of two different ways. On entering the cell, a base analogue is converted to a nucleoside triphosphate that base pairs, perhaps incorrectly, with a DNA template and is inserted into the nucleotide chain. This is one way in which the mutation can be produced. The other requires an additional round of replication so that an improper base pair forms as a result of the previously incorporated analogue. The result in both cases is a permanently modified DNA. 

Nitrous acid causes point mutations (1). For example, C is converted to U, which in the next replication pairs with A instead of G. The alteration thus becomes permanent. Mutations in which a number of nucleotides not divisible by three are inserted or removed lead to reading errors in whole segments of DNA, as they move the reading frame (frame-shift mutations). This is shown in Fig. 2 using a simple example. From the inserted C onwards, the resulting mRNA is interpreted differently during translation, producing a completely new protein sequence. 

Frameshift mutations may be produced by various mechanisms. For instance, intercalation of planar molecules, such as acridine within the DNA molecule, allows base insertions at replication. Acridine-type compounds may also induce mutations of the frameshift type by interfering with the excision and repair processes, which correct errors occurring during unequal crossover between homologous chromosomes at meiosis. Such unequal crossover gives rise to errors of the frameshift type. 

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... 

Figure 2. (continued) mutants are common (i) point mutations, (ii) insertions and (iii) deletions. Point mutations are tantamount to incorporation of an incorrect nucleotide into the growing chain and thus leave the chain length constant. Insertions consist of double or multiple copies of part of the sequence. In the case of deletions part of the sequence is omitted during replication. The chain length increases in the case of insertions and becomes smaller with deletions. 

We now turn from DNA replication to DNA mutations and repair. Several types of mutations are known (1) the substitution of one base pair for another, (2) the deletion of one or more base pairs, and (3) the insertion of one or more base pairs. The spontaneous mutation rate of T4 phage is about 10 per base per replication. E. coli aaA Drosophila melanogaster have much lower mutation rates, of the order of lO" . 

Mechanistically, the simplest type of mutagenesis occurs when the enzyme DNA polymerase is copying one strand of DNA into its complementary strand and places the incorrect nucleotide into the newly synthesized strand of DNA. Although it is thermodynamically favored that the correct base will be inserted, there is a lesser but real probability that the incorrect base will be inserted during DNA replication. An example would be placement of the wrong base, adenine (A), opposite the DNA base cytosine (C), instead of inserting the correct base guanine (G) opposite the base C. This results in what is described as a G/C to A/T transition mutation, and it is called a spontaneous mutation. 

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