UvrABC endonuclease

Four enzymes are directly involved. They are the UvrABC endonuclease, helicase, DNA polymerase I, and DNA ligase. The first cleaves the DNA strand on both sides of the pyrimidine dimer. The second enzyme removes the single-strand nucleotide segment containing the pyrimidine dimer. DNA polymerase I fills the gap with new DNA, and the nick is sealed by DNA ligase. 

In E. coli, nucleotide excision repair (Example 8.14) is carried out by the UvrABC endonuclease. The enzyme cleaves the damaged DNA strand at the seventh and third or fourth phosphodiester bonds at the 5 and 3 sides adjacent to the damaged base. The resulting oligonucleotide is removed by helicase II, and repair is carried out by DNA polymerase I and DNA ligase. 

Helicase II, the product of the uvrD gene, is also required, presumably to unwind and remove the excised oligonucleotide, which is ultimately broken down by other enzymes. The UvrABC enzyme is not a classical endonuclease, because it cuts at two distinct sites, so the term excinuclease has been proposed for it, denoting its role in excision repair. This system also repairs DNA damage that results when two strands covalently crosslink to each other. In this case, the two strands are repaired sequentially (one after the other) in order to preserve an intact template strand. 

A human excinuclease cleaves at positions -22 and +6 relative to a thymine dimer. A significant difference between this and the UvrABC enzyme is the involvement of two different endonucleases--one for cutting on the 5 side and one on the 3 side. The disease, xeroderma pigmentosum (XP), is actually a family of diseases, in which one or more enzymes of the excision pathway are deficient. The biological consequences of XP include extreme sensitivity to sunlight and a high incidence of skin cancers. In affected humans, there is at present no known way to treat the condition. 

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