UV-induced mutation hotspots occur at DNA damage hotspots.

Abstract

The frequency of UV-induced mutations at specific nucleotides along the lacI gene of Escherichia coli varies by as much as 80-fold1. The spectrum of mutations to amber, ochre, and UGA chain-terminating codons includes five hotspots accounting for over 30% of these UV-induced nonsense mutations1. The simplest explanation for the hotspot phenomenon is that the mutation frequency reflects the frequency of UV-induced DNA damage at the mutation site. To test this possibility, we measured the distribution, in a 380-base pair (bp) region of the lacI gene containing the nonsense mutation hotspots, of UV-induced cyclobutane pyrimidine dimers and pyrimidine–pyrimidine (6-4) photoproducts. The latter (also called the PydC lesion) is a UV-induced DNA lesion which occurs predominantly at TC and CC sequences2. The results reported here reveal the presence of UV-induced base damage hotspots which include the nonsense mutation hotspots. There is a linear relationship between base damage incidence and mutation incidence. The results suggest that the UV-induced pyrimidine–pyrimidine (6-4) lesion may be mutagenic.