Pyrimidine dimers result from Ultraviolet light

(a) Formation of thymine dimer. (b) Distorted DNA.

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 9).

Ultraviolet light has less energy than that of ionizing radiation and does not eject electrons and cause ionization but is nevertheless highly mutagenic. Purine and pyrimidine bases readily absorb UV light, resulting in the formation of chemical bonds between adjacent pyrimidine molecules on the same strand of DNA and in the creation of structures called pyrimidine dimers (Figure 17.24a). Pyrimidine dimers consisting of two thymine bases (called thymine dimers) are most frequent, but cytosine dimers and thymine - cytosine dimers also can form. These dimers distort the configuration of DNA (Figure 17.24b) and often block replication. Most pyrimidine dimers are immediately repaired by mechanisms discussed later in this chapter, 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—a hereditary error in the genetic instructions—to occur, the replication block must be overcome. How do bacteria and other organisms replicate despite the presence of thymine dimers?

Bacteria can 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 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 may continue and the cell survives, but only by sacrificing the normal accuracy of DNA synthesis.

The SOS system is complex, including the products of at least 25 genes. A protein called RecA binds to the damaged DNA at the blocked replication fork and becomes activated. This activation promotes the binding of a protein called LexA, which is a repressor of the SOS system. The activated RecA complex induces LexA to undergo self-cleavage, destroying its repressive activity. This inactivation enables other SOS genes to be expressed, and the products of these genes allow replication of the damaged DNA to proceed. The SOS system allows bases to be inserted into a new DNA strand in the absence of bases on the template strand, but these insertions result in numerous errors in the base sequence.

Eukaryotic cells have a specialized DNA polymerase called polymerase ^ (eta) that bypasses pyrimidine dimers. Polymerase ^ preferentially inserts AA opposite a pyrimi-dine dimer. This strategy seems to be reasonable because about two-thirds of pyrimidine dimers are thymine dimers. However, the insertion of AA opposite a CT dimer results in a C-G:A-T transversion. Polymerase ^ is therefore said to be an error-prone polymerase.

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