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