Zdzienicka M Z, Venema J, Mitchell D L, van Hoffen A, van Zeeland A A, Vrieling H, Mullenders L H, Lohman P H, Simons J W
MGC-Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
Mutat Res. 1992 Jan;273(1):73-83. doi: 10.1016/0921-8777(92)90051-4.
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.
分离并鉴定了对紫外线敏感的中国仓鼠V79细胞突变体V-H1（互补组2）的部分回复体（RH1-26）。它被用于分析两种主要的紫外线诱导损伤——环丁烷嘧啶二聚体和（6-4）光产物的诱变效力。V-H1和RH1-26在整个基因组以及活性hprt基因中都不能修复嘧啶二聚体。V-H1中从整个基因组修复（6-4）光产物的速度比野生型V79细胞慢，但在RH1-26中恢复到正常水平。尽管V-H1细胞的诱变性增强了7倍，但RH1-26细胞尽管缺乏嘧啶二聚体修复能力，其紫外线诱导的诱变水平仍略低于野生型V79细胞。V79和RH1-26细胞中hprt突变的分子性质和DNA链特异性相似，但与V-H1细胞不同。由于在RH1-26以及V79细胞中，大多数hprt突变是由非转录DNA链中的损伤诱导的，而在V-H1中是由转录DNA链中的损伤诱导的，观察到的突变链偏向表明，正常情况下（6-4）光产物在转录DNA链中优先被修复。V-H1中受损的（6-4）光产物修复对紫外线诱导的突变性和hprt突变的分子性质产生的显著影响表明，（6-4）光产物是主要的紫外线诱导诱变损伤。
