What Are the Chances That Your Dna Could Happen Again
Incorrectly paired nucleotides that still remain following mismatch repair become permanent mutations after the next cell division. This is because once such mistakes are established, the cell no longer recognizes them as errors. Consider the case of wobble-induced replication errors. When these mistakes are not corrected, the incorrectly sequenced DNA strand serves as a template for future replication events, causing all the base-pairings thereafter to be wrong. For instance, in the lower half of Figure 2, the original strand had a C-G pair; then, during replication, cytosine (C) is incorrectly matched to adenine (A) because of wobble. In this example, wobble occurs because A has an extra hydrogen atom. In the next round of cell division, the double strand with the C-A pairing would separate during replication, each strand serving as a template for synthesis of a new DNA molecule. At that particular spot, C would pair with G, forming a double helix with the same sequence as its original (i.e., before the wobble occurred), but A would pair with T, forming a new DNA molecule with an A-T pair in place of the original C-G pair. This type of mutation is known as a base, or base-pair, substitution. Base substitutions involving replacement of one purine for another or one pyrimidine for another (e.g., a mismatched A-A pair, instead of A-T) are known as transitions; the replacement of a purine by a pyrimidine, or vice versa, is called a transversion.
Likewise, when strand-slippage replication errors are not corrected, they become insertion and deletion mutations. Much of the early research on strand-slippage mutations was conducted by George Streisinger in the 1970s. Streisinger, a professor at the University of Oregon and a fish hobbyist, is known by some as the "founding father of zebrafish research." However, he is also known for his work with phage T4, a bacterial virus. Streisinger used this virus to show that most nucleotide insertion and deletion mutations occur in areas of DNA that contain many repeated sequences (also called tandem repeats), and he formulated the strand-slippage hypothesis to explain why this was the case (Streisinger et al., 1966). (In Figure 3, notice the series of repeat T's on the template strand where the slippage has occurred.) When slippage takes place, the presence of nearby duplicate bases stabilizes the slippage so that replication can proceed. During the next round of replication, when the two strands separate, the insertion or deletion on either the template or primer strand, respectively, will be perpetuated as a permanent mutation. Scientists have collected enough evidence to confirm Streisinger's strand-slippage hypothesis, and this type of mutagenesis remains an active field of scientific research.
Figure 3: Strand slippage during DNA replication.
When strand slippage occurs during DNA replication, a DNA strand may loop out, resulting in the addition or deletion of a nucleotide on the newly-synthesized strand.
© 2014 Nature Education Adapted from Pierce, Benjamin. Genetics: A Conceptual Approach, 2nd ed. All rights reserved. 
Although most mutations are believed to be caused by replication errors, they can also be caused by various environmentally induced and spontaneous changes to DNA that occur prior to replication but are perpetuated in the same way as unfixed replication errors. As with replication errors, most environmentally induced DNA damage is repaired, resulting in fewer than 1 out of every 1,000 chemically induced lesions actually becoming permanent mutations. The same is true of so-called spontaneous mutations. "Spontaneous" refers to the fact that the changes occur in the absence of chemical, radiation, or other environmental damage. Rather, they are usually caused by normal chemical reactions that go on in cells, such as hydrolysis. These types of errors include depurination, which occurs when the bond connecting a purine to its deoxyribose sugar is broken by a molecule of water, resulting in a purine-free nucleotide that can't act as a template during DNA replication, and deamination, which results in the loss of an amino group from a nucleotide, again by reaction with water. Again, most of these spontaneous errors are corrected by DNA repair processes. But if this does not occur, a nucleotide that is added to the newly synthesized strand can become a permanent mutation.
Source: http://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409
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