DNA Repair : Nucleotide excision repair

Exposure of a cell to UV radiation can result in the covalent joining of two adjacent pyrimidines (usually thymines), producing a dimer. These intrastrand cross-links prevent DNA pol from replicating the DNA strand beyond the site of dimer formation. Thymine dimers are excised in bacteria by UvrABC proteins in a process known as nucleotide excision repair (NER), as illustrated in Figure 1. A related pathway is present in humans . [Note: Transcription-coupled repair, a type of NER, fixes DNA lesions encountered during RNA synthesis.]

Figure 1:  Nucleotide excision repair of pyrimidine dimers in Escherichia coli DNA. UV = ultraviolet.
1. Recognition and excision of UV-induced dimers: A UV-specific endonuclease (called uvrABC excinuclease) recognizes the bulky dimer and cleaves the damaged strand on both the 5′-side and 3′-side of the lesion. A short oligonucleotide containing the dimer is excised, leaving a gap in the DNA strand. This gap is filled in using a DNA pol I and DNA ligase. NER occurs throughout the cell cycle.
2. UV radiation and cancer: Pyrimidine dimers can be formed in the skin cells of humans exposed to UV radiation in unfiltered sunlight. In the rare genetic disease xeroderma pigmentosum (XP), the cells cannot repair the damaged DNA, resulting in extensive accumulation of mutations and, consequently, early and numerous skin cancers (Fig.2). XP can be caused by defects in any of the several genes that code for the XP proteins required for NER of UV damage in humans.

Figure 2:  Patient with xeroderma pigmentosum.

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