Nucleic Acids Research, 2003, Vol. 31, No. 20 5897-5906
© 2003 Oxford University Press
Effects of genomic context and chromatin structure on transcription-coupled and global genomic repair in mammalian cells
1 Department of Environmental Medicine, 3 Department of Medicine and 4 Department of Pathology, New York University School of Medicine, Tuxedo, NY 10987, USA and 2 Department of Biological Sciences, Columbia University, New York, NY 10027, USA
*To whom correspondence should be addressed. Tel: +1 845 731 3585; Fax: +1 845 351 2385; Email: tang{at}env.med.nyu.edu
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
It has been long recognized that in mammalian cells, DNA damage is preferentially repaired in the transcribed strand of transcriptionally active genes. However, recently, we found that in Chinese hamster ovary (CHO) cells, UV-induced cyclobutane pyrimidine dimers (CPDs) are preferentially repaired in both the transcribed and the non-transcribed strand of exon 1 of the dihydrofolate reductase (DHFR) gene. We mapped CPD repair at the nucleotide level in the transcriptionally active DHFR gene and the adjacent upstream OST gene, both of which have been translocated to two chromosomal positions that differ from their normal endogeneous positions. This allowed us to study the role of transcription, genomic context and chromatin structure on repair. We found that CPD repair in the transcribed strand is the same for endogenous and translocated DHFR genes, and the order of repair efficiency is exon 1 > exon 2 > exon 5. However, unlike the endogenous DHFR gene, efficient repair of CPDs in the non-transcribed strand of exon 1 is not observed in the translocated DHFR gene. CPDs are efficiently repaired in the transcribed strand in endogenous and translocated OST genes, which indicates that efficient repair in exon 1 of the non-transcribed strand of the endogenous DHFR gene is not due to the extension of transcription-coupled repair of the OST gene. Using micrococcal nuclease digestion, we probed the chromatin structure in the DHFR gene and found that chromatin structure in the exon 1 region of endogenous DHFR is much more open than at translocated loci. These results suggest that while transcription-coupled repair is transcription dependent, global genomic repair is greatly affected by chromatin structure.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Episkopou, S. A. Kyrtopoulos, P. P. Sfikakis, M. Fousteri, M. A. Dimopoulos, L. H.F. Mullenders, and V. L. Souliotis Association between Transcriptional Activity, Local Chromatin Structure, and the Efficiencies of Both Subpathways of Nucleotide Excision Repair of Melphalan Adducts Cancer Res., May 15, 2009; 69(10): 4424 - 4433. [Abstract] [Full Text] [PDF]
|
|