(6-4) photoproducts and not cyclobutane pyrimidine dimers are the main UV-induced mutagenic lesions in Chinese hamster cells.
A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant V-H1 (complementation group 2) was isolated and characterized. It was used to analyze the mutagenic potency of the 2 major UV-induced lesions, cyclobutane pyrimidine dimers and (6-4) photoproducts. Both V-H1 and RH1-26 did not repair pyrimidine dimers measured in the genome overall as well as in the active hprt gene. Repair of (6-4) photoproducts from the genome overall was slower in V-H1 than in wild-type V79 cells, but was restored to normal in RH1-26. Although V-H1 cells have a 7-fold enhanced mutagenicity, RH1-26 cells, despite the absence of pyrimidine dimer repair, have a slightly lower level of UV-induced mutagenesis than observed in wild-type V79 cells. The molecular nature of hprt mutations and the DNA-strand specificity were similar in V79 and RH1-26 cells but different from that of V-H1 cells. Since in RH1-26 as well as in V79 cells most hprt mutations were induced by lesions in the non-transcribed DNA strand, in contrast to the transcribed DNA strand in V-H1, the observed mutation-strand bias suggests that normally (6-4) photoproducts are preferentially repaired in the transcribed DNA strand. The dramatic influence of the impaired (6-4) photoproduct repair in V-H1 on UV-induced mutability and the molecular nature of hprt mutations indicate that the (6-4) photoproduct is the main UV-induced mutagenic lesion.
Zdzienicka
M Z
MZ
MGC-Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
Venema
J
J
Mitchell
D L
DL
van Hoffen
A
A
van Zeeland
A A
AA
Vrieling
H
H
Mullenders
L H
LH
Lohman
P H
PH
Simons
J W
JW
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003503:Cyclobutanes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004260:DNA Repair; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010777:Photochemistry; D011740:Pyrimidine Dimers; D011744:Pyrimidinones / Q000737:chemistry; D014466:Ultraviolet Rays
D003503:Cyclobutanes; D011740:Pyrimidine Dimers; D011744:Pyrimidinones; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase