The formation of DNA photoproducts by ultraviolet (UV) light is respon
sible for the induction of mutations and the development of skin cance
r. Cis-syn cyclobutane pyrimidine dimers (pyrimidine dimers) are the m
ost frequent lesions produced in DNA by UV irradiation. Besides being
mutagenic, pyrimidine dimers may interfere with other important DNA-de
pendent processes. To analyze the effects of pyrimidine dimers on the
ability of DNA sequences to be recognized by trans-acting factors, we
have incorporated site-specific T boolean AND T dimers into oligonucle
otides containing the recognition sequences of the sequence-specific t
ranscription factors E2F, NF-Y, AP-1, NF kappa B, and p53. In each cas
e, presence of the photodimer strongly inhibited binding of the respec
tive transcription factor complex; Reduction of binding varied between
11- and 60-fold. The results indicate that the most common UV-induced
DNA lesion can interfere severely with binding of several important c
ell cycle regulatory and DNA damage responsive transcription factors.
We suggest that inhibition of transcription factor binding may be a ma
jor biological effect of UV radiation since promoter regions are known
to be repaired inefficiently and since UV damage can deregulate the f
unction of a large number of different factors.