Nucleotide Excision Repair

The final repair pathway that we'll consider is nucleotide-excision repair, which removes bulky DNA lesions that distort the double helix, such as pyrimidine dimers or large hydrocarbons attached to the DNA. Nucleotide-excision repair is quite versatile and can repair many different types of DNA damage. It is found in cells of all organisms from bacteria to humans and is one of the most important of all repair mechanisms.

The process of nucleotide excision is complex; in humans, a large number of genes take part. First, a complex of enzymes scans DNA, looking for distortions of its three-dimensional configuration (Figure 17.30a and b). When a distortion is detected, additional enzymes separate the two nucleotide strands at the damaged region, and single-strand-binding proteins stabilize the separated strands (Figure 17.30c). Next, the sugar-phosphate backbone of the damaged strand is cleaved on both sides of the damage. One cut is made 5 nucleotides upstream (on the 3' side) of the damage, and the other cut is made 8 nucleotides (in prokaryotes) or from 21 to 23 nucleotides (in eukaryotes) downstream (on the 5' side) of the damage (Figure 17.30d). Part of the damaged strand is peeled away (< Figure 17.30e), and the gap is filled in by DNA polymerase and sealed by DNA ligase (< Figure 17.30f).

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