Excision Repair of Bulky Lesions in the DNA of Mammalian Cells
Although the excision of pyrimidine dimers from UV-irradiated human cells has been known since 1968 (1) and excision has been the subject of a number of symposia and recent reviews (2–4), the details of the process still elude us. We assume that the excision of pyrimidine dimers is of the nucleotide excision type, (a) by analogy with bacteria, (b) because it is of the large patch type, (c) because although few single strand breaks accumulate during excision in normal human cells, the numbers that accumulate in excision defective cells are much less, (d) because the introduction of an exogenous UV endonuclease enhances repair and survival in excision defective cells and (e) because inhibitors of the polymerization steps such as hydroxyurea and cytosine arabinoside result in the accumulation of single strand breaks (5, 6). (However, the number of breaks observed is much less than the number of dimers removed in uninhibited cells, indicating that the various steps in excision repair act as if they are linked to one another (7).) The various measures of excision repair of pyrimidine dimers — the best studied lesion to date because they are easy to identify and measure in a number of ways — give general agreeement (8)but different investigators obtain conflicting results in details such as the dependence on time, dose and the method of measurement (9–11). Nevertheless, the various techniques indicate that excision repair of dimers varies widely among cell lines and strains. For example, rodent cells are low excisers compared to normal human cells (12), and among humans the cells of most of the individuals with xeroderma pigmentosum (XP) are defective in excision repair (13).
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