| Comments |
P.282 right column 2nd paragraph: "Quantitative estimates of spontaneous DNA degradation in cells suggest that the daily dose of promutagenic damage is substantial [refs 97–99] (Fig. 3A). These lesions result from the intrinsic chemical instability of DNA under physiological conditions and the exposure of DNA to active oxygen and other reactive metabolites and coenzymes that are generated by normal cells [refs 97,99]. Altogether, it is estimated that ∼20,000 potentially mutagenic lesions arise per diploid mammalian cell per day. Most of these lesions are repaired by the base excision repair (BER) pathway [refs 68,69]. This repair must occur efficiently prior to DNA replication for cells to maintain a low spontaneous mutation rate. The toll of 20,000 spontaneous lesions per cell per day is high, and this is in addition to the 100,000–1,000,000 DNA polymerase errors that occur in replicating cells over the same approximate time frame (Fig. 3B)." |