In 1927, Hermann Muller demonstrated that mutations in fruit flies could be induced by X-rays. The results of subsequent studies showed that X-rays greatly increase mutation rates in all organisms. Because of their high energies, X-rays, gamma rays, and cosmic rays are all capable of penetrating tissues and damaging DNA. These forms of radiation, called ionizing radiation, dislodge electrons from the atoms that they encounter, changing stable molecules into free radicals and reactive ions, which then alter the structures of bases and break phosphodiester bonds in DNA. Ionizing radiation also frequently results in double-strand breaks in DNA. Attempts to repair these breaks can produce chromosome mutations (discussed in Chapter 6).

Ultraviolet (UV) light has less energy than ionizing radiation and does not eject electrons, but is nevertheless highly mutagenic. Pyrimidine bases readily absorb UV light, resulting in the formation of chemical bonds between adjacent pyrimidine molecules on the same strand of DNA, which create pyrimidine dimers (Figure 13.20a). Pyrimidine dimers consisting of two thymine bases (called thymine dimers) are most frequent, but cytosine dimers and thymine–cytosine dimers can also form. These dimers are bulky lesions that distort the configuration of DNA (Figure 13.20b) and often block replication. Most pyrimidine dimers are immediately repaired by mechanisms discussed in Section 13.4, but some escape repair and inhibit replication and transcription.

When pyrimidine dimers block replication, cell division is inhibited and the cell usually dies; for this reason, UV light kills bacteria and is an effective sterilizing agent. For a mutation to occur, the replication block must be overcome. Bacteria can sometimes circumvent replication blocks produced by pyrimidine dimers and other types of DNA damage by means of the SOS system. This system allows replication blocks to be overcome, but in the process, it makes numerous mistakes and greatly increases the rate of mutation. Indeed, the very reason that replication can proceed in the presence of a block is that the enzymes in the SOS system do not strictly adhere to the base-pairing rules. The trade-off is that replication can continue and the cell survives, but only by sacrificing the normal accuracy of DNA synthesis.

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