Specificity of UV-induced mutations at an endogenous locus in mammalian cells
We have used a rapid in vivo recombinational method to clone and completely sequence 34 UV-induced mutants at the adenine phosphoribosyltransferase (APRT) locus of Chinese hamster ovary cells. Among the mutants recovered, 26 were single base substitutions including 17 G.C----A.T transitions and a single A.T----G.C transition. Three of the 4 possible transversions accounted for the remaining 8 mutations. The G.C----T.A transversion was not recovered. Six tandem double or closely neighboring double-base substitutions, one double mutation consisting of a G.C----T.A transversion and an adjacent frameshift, as well as one single frameshift mutation were also recovered. UV-induced mutation appears to be targeted to dipyrimidine sites with only two exceptions. These include two double mutations where only one of the base substitutions occurred at a dipyrimidine site. The observed specificity of UV-light-induced mutations at the APRT locus is consistent with the argument that G.C----A.T transitions result primarily from the (6-4) pyrimidine pyrimidone lesion. A striking resemblance in the distribution of UV-induced mutants and a collection of 30 spontaneous mutants identified recently in our laboratory was noted. Both share a common strong site of multiple occurrence and a considerable degree of overlap with respect to site specificity. We speculate therefore that DNA context plays a significant role in mutation fixation in mammalian cells.
- Research Organization:
- York Univ., Toronto, Ontario
- OSTI ID:
- 5468104
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:24
- Country of Publication:
- United States
- Language:
- English
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CHO CELLS
GENETIC RADIATION EFFECTS
MUTATIONS
RADIOINDUCTION
SPECIFICITY
AMINO ACID SEQUENCE
CLONING
HAMSTERS
RADIATION INDUCED MUTANTS
ULTRAVIOLET RADIATION
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
MAMMALS
MOLECULAR STRUCTURE
MUTANTS
RADIATION EFFECTS
RADIATIONS
RODENTS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture