UV-induced G:C-->A:T transitions at the APRT locus of Chinese hamster ovary cells cluster at frequently damaged 5'-TCC-3' sequences.
We have determined the relative frequency in vitro of UV-induced cyclobutane pyrimidine dimers (py <> py) and (6-4) pyrimidine pyrimidone photoproducts (py(6-4)pyo) at individual sites in selected regions of the Chinese hamster ovary (CHO) adenine phosphoribosyltransferase (aprt) gene, and compared this to the observed specificity of UV-induced mutations (Drobetsky et al., 1987, 1989). Our results indicate that G:C-->A:T transition "hotspots" (multiple occurrences) at the chromosomal CHO aprt locus, the majority of which occur at 5'TCC-3', are clearly targeted at sites associated with a relatively high yield of py <> py and/or py(6-4)pyo. We conclude that photoproduct frequency plays a major role in UV-induced transition mutagenesis at 5'-TCC-3' sites at an endogenous locus in a rodent cell line, and that both py(6-4)pyo and py <> py have premutagenic potential.
Drobetsky
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Institut Curie, Section de Biologie, CNRS URA 1292, Paris, France.
Sage
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D000228:Adenine Phosphoribosyltransferase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003503:Cyclobutanes / Q000737:chemistry; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004252:DNA Mutational Analysis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010777:Photochemistry; D017354:Point Mutation; D011740:Pyrimidine Dimers; D011744:Pyrimidinones / Q000737:chemistry; D014466:Ultraviolet Rays
D003503:Cyclobutanes; D011740:Pyrimidine Dimers; D011744:Pyrimidinones; D004247:DNA; D000228:Adenine Phosphoribosyltransferase