Enhanced UV-induced mutagenesis in the UV61 cell line, the Chinese hamster homologue of Cockayne's syndrome B, is associated with defective transcription coupled repair of cyclobutane pyrimidine dimers.
Cells from Cockayne's syndrome (CS) patients are hypersensitive to the cytotoxic effects of UV-irradiation and are defective in transcription coupled repair (TCR). We have examined the mutagenic consequences of impaired TCR in the Chinese hamster cell line UV61, the rodent homologue of CS complementation group B. Analysis of the two major UV-induced photolesions, cyclobutane pyrimidine dimers (CPD) and pyrimidine 6-4 pyrimidone photoproducts (6-4 PP), revealed that repair of CPD from the transcribed strand was strongly reduced in UV61 cells, but repair of 6-4 PP was indistinguishable from that in wild-type hamster cells. UV-induced mutation induction was enhanced in UV61 compared to that observed in repair proficient cells. The spectrum of UV-induced base substitutions in UV61 was clearly different from that observed in wild-type hamster cells and resembled the spectrum previously observed in nucleotide excision repair deficient hamster cells. In UV61 cells a strong strand bias for mutation induction was found; assuming that premutagenic lesions occur at dipyrimidine sequences, 76% of the mutations could be attributed to lesions in the transcribed strand. These data strongly favour the hypothesis that defective TCR of CPD is responsible for the enhanced UV-induced mutagenesis in UV61 cells.
Vreeswijk
M P
MP
MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Centre, Netherlands.
Overkamp
M W
MW
Westland
B E
BE
van Hees-Stuivenberg
S
S
Vrieling
H
H
Zdzienicka
M Z
MZ
van Zeeland
A A
AA
Mullenders
L H
LH
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002470:Cell Survival / Q000528:radiation effects; D003057:Cockayne Syndrome / Q000235:genetics* / Q000378:metabolism*; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D016296:Mutagenesis; D011740:Pyrimidine Dimers / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D012313:RNA / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000235:genetics; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D012313:RNA; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase