Cyclobutane pyrimidine dimers and bulky chemical DNA adducts are efficiently repaired in both strands of either a transcriptionally active or promoter-deleted APRT gene.
Both prokaryotic and eukaryotic cells have the capacity to repair DNA damage preferentially in the transcribed strand of actively expressed genes. However, we have found that several types of DNA damage, including cyclobutane pyrimidine dimers (CPDs) are repaired with equal efficiency in both the transcribed and nontranscribed strands of the adenine phosphoribosyltransferase (APRT) gene in Chinese hamster ovary cells. We further found that, in two mutant cell lines in which the entire APRT promoter region has been deleted, CPDs are still efficiently repaired in both strands of the promoterless APRT gene, even though neither strand appears to be transcribed. These results suggest that efficient repair of both strands at this locus does not require transcription of the APRT gene. We have also mapped CPD repair in exon 3 of the APRT gene in each cell line at single nucleotide resolution. Again, we found similar rates of CPD repair in both strands of the APRT gene domain in both APRT promoter-deletion mutants and their parental cell line. Our findings suggest that current models of transcription-coupled repair and global genomic repair may underestimate the importance of factors other than transcription in governing the efficiency of nucleotide excision repair.
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA.
Y
Y
Zheng
A
A
Pao
G M
GM
Adair
M
M
Tang
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000228:Adenine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000378:metabolism; D029968:Escherichia coli Proteins; D005091:Exons; D007700:Kinetics; D011401:Promoter Regions, Genetic; D011740:Pyrimidine Dimers / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014162:Transfection; D014466:Ultraviolet Rays
D018736:DNA Adducts; D029968:Escherichia coli Proteins; D011740:Pyrimidine Dimers; D012333:RNA, Messenger; D011994:Recombinant Proteins; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D000228:Adenine Phosphoribosyltransferase; D004706:Endodeoxyribonucleases; C036385:endodeoxyribonuclease uvrABC