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Originally published In Press as doi:10.1074/jbc.M010973200 on February 13, 2001

J. Biol. Chem., Vol. 276, Issue 20, 16786-16796, May 18, 2001
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Cyclobutane Pyrimidine Dimers and Bulky Chemical DNA Adducts Are Efficiently Repaired in Both Strands of Either a Transcriptionally Active or Promoter-deleted APRT Gene*

Yi ZhengDagger §, Annie PaoDagger §, Gerald M. AdairDagger , and Moon-shong TangDagger

From the Dagger  Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957 and the  Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987

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.


* This work was supported by United States Public Health Services Grants ES03124, ES08389 (to M.-s. T.) and GM56165 (to G. M. A.) from the National Institutes of Health (NIH), and service core support from NIEHS, NIH Center Grants ES077784 and ES00260.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

To whom correspondence should be addressed: Tel.: 845-731-3585; Fax: 845-351-3492; E-mail: tang@env.med.nyu.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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