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. 1993 May 25;21(10):2355–2361. doi: 10.1093/nar/21.10.2355

Cyclobutane thymine dimers in a ras proto-oncogene hot spot activate the gene by point mutation.

H Kamiya 1, N Murata 1, T Murata 1, S Iwai 1, A Matsukage 1, C Masutani 1, F Hanaoka 1, E Ohtsuka 1
PMCID: PMC309532  PMID: 8389438

Abstract

ras proto-oncogenes with a cyclobutane-type thymine photodimer (cis-syn or trans-syn isomer) were constructed by replacement of a portion of the gene with a chemically synthesized fragment. When the genes were transfected by the calcium phosphate method into mouse NIH3T3 cells, they induced focus-formation, indicating that both photoproducts were mutagenic in mammalian cells. Sequence analysis of the ras gene fragments derived from the transformed cells showed that the genes were activated by a point mutation. The mutations detected most frequently were 3'-T-->A for the cis-syn isomer and 5'-T-->A for the trans-syn isomer. In contrast, a different trend of mutations was observed when a primer on a DNA template with a cis-syn dimer was extended in vitro by either DNA polymerase beta or alpha.

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