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The ratio of (6-4) photoproducts to (6-4) and (6-4) photoproducts coupled to cytosine was found to vary from 0 to 30% depending on the cell line, irradiation time, and the presence of photoreactivating enzyme. In addition, it was found that the ratio increased sharply with the passage of time. The accumulation of (6-4) photoproducts in both human and yeast cells is a result of the slow repair of (6-4) photoproducts, a characteristic of global genomic hypermutation.
However, rather than being solely a problem of DNA repair, there may also be some contribution from increased DNA synthesis, because in a study in which the excision repair of dimers derived from the two different (6-4) photoproducts was measured, it was found that the excision of the (6-4) photoproduct arising from the chloro-substituted thymine was reduced to only 40% of that of the excision of the (6-4) photoproduct derived from thymine. It is further noted that the excision of these lesions by E. coli endonuclease III was significantly enhanced by factors 3 and 6 whereas the excision by E. coli endonuclease VIII was not significantly increased by factors 3 or 6. The UV-induced excision of the (6-4) photoproduct derived from chlorothymidine was only slightly enhanced by E. coli endonuclease III.
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