There are elaborate DNA repair processes designed to recognize and repair different types of DNA lesions. It is important to note that DNA damage, in and of itself, does not necessarily lead to the formation of a mutation in the DNA. Different mutagens have a different modes of damaging DNA and are discussed further in the next section. Typical mutagens include chemicals, like those inhaled while smoking, and radiation, such as X-rays, ultraviolet light, and nuclear radiation. When a mutation is caused by an environmental factor or a chemical agent, that agent is called a mutagen. He induced mutagenesis by irradiating fruit flies with X-rays. In 1927, Hermann Muller first demonstrated the effects of mutations with observable changes in chromosomes. Harmful mutations can lead to cancer and various heritable diseases, but beneficial mutations are the driving force of evolution. In nature, mutagenesis, or the process of generating DNA mutations, can lead to changes that are harmful, or beneficial, or have no effect. Mutations may also occur during the processes of mitosis and meiosis when sister chromatids and/or homologous chromosomes are being separated from one another. Larger lesions or cross-links in the DNA during replication can lead to more catastrophic DNA damage including DNA strand breaks. DNA polymerases can also slip during the replication of regions of the DNA that have repeated sequences or large stretches repeating a single base. Sometimes lesions may cause bases to be skipped during replication or cause extra nucleotides to be inserted into the backbone. Whereas, a transversion refers to the substitution of a purine for a pyrimidine or vice versa. This can lead to the formation of transition or transversion mutations.Ī transition mutation is a point mutation that changes a purine nucleotide to another purine (A ↔ G) or a pyrimidine nucleotide to another pyrimidine (C ↔ T). For example, an adenine-containing nucleotide will often be added across a lesion, regardless of what the correct match should be. If a DNA polymerase encounters a damaged DNA base in the template DNA during replication it may place a random nucleotide base across from the lesion. The next section will highlight common types of DNA damage and their effects. DNA mutations can also result through the replication of DNA that has been damaged by endogenous or exogenous agents. Even with such high fidelity, this error rate will lead to between 3 and 3,000 errors within the human genome for each cell undergoing DNA replication. With these safeguards, their error rates are typically very low and range from one in a million bases to one in a billion bases. ![]() As noted in chapter 9, DNA polymerases are highly processive enzymes that contain proofreading and editing functions. For example, DNA mutations can be caused by mistakes made by the DNA polymerase during replication. They can be large scale, altering the structure of the chromosomes, or small scale where they only alter a few or even a single base or nucleotide. Mutations are random changes that occur within the sequence of bases in DNA.
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