In spite of the rules of base-pairing, sometimes mistakes are made during DNA replication. Mistakes occur about once in every 10,000 base pairs and can potentially be disastrous for an organism. There are various repair mechanisms that can fix these errors, and, in the end, the observed error rate is very low (often less than one mistake/10 million bases). Mismatch repair occurs when DNA polymerase and other proofreading enzymes remove incorrectly paired nucleotides. Excision repair involves the removal of damaged nucleotides from a DNA molecule.
If these repair mechanisms are not successful, mutations occur. A mutation is a permanent change in an organism's DNA. If the mutation occurs in a reproductive cell, the mutation can be passed to future generations and potentially become established in a population (this is why mutations are the ultimate source of genetic variation in populations). The effect that a mutation has on an organism depends upon whether or not the mutation occurs in a gene and, if it does occur in a gene, how much it changes the resulting protein. Therefore, mutations can be harmful (e.g., sickle cell anemia, cystic fibrosis), beneficial (e.g., antibiotic resistance), or neutral (a neutral mutation occurs when an organism's DNA sequence changes but this change has no effect on the organism's phenotype).
An example of enzymes that help defend against mutations are specific DNA polymerases that fix errors that occur in DNA as a result of exposure to UV radiation (sunlight). One type of damage that UV radiation causes in DNA is the creation of thymine dimers. Thymine dimers result when two thymine bases are next to each other in a DNA strand and they covalently bond to each other instead of hydrogen bond to the adenine on the complementary strand. If this error occurs in part of the DNA that regulates the cell cycle, skin cancer can result.
Xeroderma pigmentosum (XP) is an autosomal recessive genetic condition that occurs as a result of a mutation to one of seven different DNA polymerases that repair UV-damaged DNA. The affected individual has a decreased ability to repair UV-induced mutations and the resulting damage is cumulative and irreversible. These individuals must stay away from sunlight and are sometimes referred to as "Children of the Night". People with XP begin developing skin cancers in childhood and life expectancy is significantly decreased.