| Autor: |
Vreeswijk MP; MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Centre, Netherlands., Overkamp MW, Westland BE, van Hees-Stuivenberg S, Vrieling H, Zdzienicka MZ, van Zeeland AA, Mullenders LH |
| Jazyk: |
angličtina |
| Zdroj: |
Mutation research [Mutat Res] 1998 Oct 21; Vol. 409 (1), pp. 49-56. |
| DOI: |
10.1016/s0921-8777(98)00038-x |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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