Increased UV resistance of a xeroderma pigmentosum revertant cell line is correlated with selective repair of the transcribed strand of an expressed gene.
A UV-resistant revertant (XP129) of a xeroderma pigmentosum group A cell line has been reported to be totally deficient in repair of cyclobutane pyrimidine dimers (CPDs) but proficient in repair of 6-4 photoproducts. This finding has been interpreted to mean that CPDs play no role in cell killing by UV. We have analyzed the fine structure of repair of CPDs in the dihydrofolate reductase gene in the revertant. In this essential, active gene, we observe that repair of the transcribed strand is as efficient as that in normal, repair-proficient human cells, but repair of the nontranscribed strand is not. Within 4 h after UV at 7.5 J/m2, over 50% of the CPDs were removed, and by 8 h, 80% of the CPDs were removed. In contrast, there was essentially no removal from the nontranscribed strand even by 24 h. Our results demonstrate that overall repair measurements can be misleading, and they support the hypothesis that removal of CPDs from the transcribed strands of expressed genes is essential for UV resistance.
Lommel
L
L
Department of Biological Sciences, Stanford University, California 94305-5020.
Hanawalt
P C
PC
D000818:Animals; D002461:Cell Line, Transformed; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D015247:Deoxyribonuclease HindIII / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011740:Pyrimidine Dimers; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics*
D011740:Pyrimidine Dimers; D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase; D015247:Deoxyribonuclease HindIII; D015252:Deoxyribonucleases, Type II Site-Specific; C029312:GGTACC-specific type II deoxyribonucleases