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Nucleotide Excision Repair - Base excision can repair only one base pair change whereas bulky base damage including thymine dimers are removed by nucleotide excision repair. If the dimerization is not reversed by the photo reactivation system, then nucleotide excision repair comes into picture. Two copies of the protein product of the uvrA gene combines with one copy of the product of the uvrB gene to form a uvrA2-uvrB complex that moves along the DNA, looking for damage.

When the complex finds damage such as a thymine dimer, with moderate, to large distortion of the DNA double helix, the uvrA2 dimer dissociates, leaving the uvrB subunit alone.

This causes the DNA to bend and attract the protein product of the uvrC gene, uvrC. Binding of uvrC protein causes a conformational change in the DNA following uvrB to nick the DNA four to five nucleotides on the 3' side of the lesion. After the 3' nicking by uvrB, uvrC protein nicks 5 bp away, towards the 5' end.

The binding of uvrC and nicking reactions require A TP binding but not hydrolysis. The three components, uvrA, uvrB and uvrC, are together called the ABC exonuclease. The enzyme helicase- II, the product of the uvrD gene, then removes the 12-13 nucleotides along with uvrC.

DNA polymerase I fills in the gap and in the process, evicts the uvrB and DNA ligase close to the remaining nick. This is another relatively simple system designed to detect helix distortions and repair them like base excision repair. Nucleotide excision repair is present in all organisms.