DNA strand specificity for UV-induced mutations in mammalian cells
- State Univ. of Leiden (Netherlands)
The influence of DNA repair on the molecular nature of mutations induced by UV light (254 nm) was investigated in UV-induced hprt mutants from UV-sensitive Chinese hamster cells (V-H1) and the parental line (V79). The nature of point mutations in hprt exon sequences was determined for 19 hprt mutants of V79 and for 17 hprt mutants of V-H1 cells by sequence analysis of in vitro-amplified hprt cDNA. The mutation spectrum in V79 cells consisted of single- and tandem double-base pair changes, while in V-H1 cells three frameshift mutations were also detected. All base pair changes in V-H1 mutants were due to GC----AT transitions. In contrast, in V79 all possible classes of base pair changes except the GC----CG transversion were present. In this group, 70% of the mutations were transversions. Since all mutations except one did occur at dipyrimidine sites, the assumption was made that they were caused by UV-induced photoproducts at these sites. In V79 cells, 11 out of 17 base pair changes were caused by photoproducts in the nontranscribed strand of the hprt gene. However, in V-H1 cells, which are completely deficient in the removal of pyrimidine dimers from the hprt gene and which show a UV-induced mutation frequency enhanced seven times, 10 out of 11 base pair changes were caused by photoproducts in the transcribed strand of the hprt gene. We hypothesize that this extreme strand specificity in V-H1 cells is due to differences in fidelity of DNA replication of the leading and the lagging strand. Furthermore, we propose that in normal V79 cells two processes determine the strand specificity of UV-induced mutations in the hprt gene, namely preferential repair of the transcribed strand of the hprt gene and a higher fidelity of DNA replication of the nontranscribed strand compared with the transcribed strand.
- OSTI ID:
- 5401491
- Journal Information:
- Molecular and Cellular Biology; (USA), Journal Name: Molecular and Cellular Biology; (USA) Vol. 9:3; ISSN MCEBD; ISSN 0270-7306
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACID SEQUENCE
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHO CELLS
DNA
DNA REPAIR
ELECTROMAGNETIC RADIATION
ENZYMES
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
GLYCOSYL TRANSFERASES
HAMSTERS
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
MAMMALS
MOLECULAR STRUCTURE
MUTATION FREQUENCY
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PENTOSYL TRANSFERASES
PYRIMIDINE DIMERS
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RADIOSENSITIVITY
RECOVERY
REPAIR
RODENTS
TRANSCRIPTION
TRANSFERASES
ULTRAVIOLET RADIATION
VERTEBRATES