This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nouspikel, T. P.
Right arrow Articles by Hanawalt, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nouspikel, T. P.
Right arrow Articles by Hanawalt, P. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2006, p. 8722-8730, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.01263-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcription Domain-Associated Repair in Human Cells{triangledown}

Thierry P. Nouspikel,1,2* Nevila Hyka-Nouspikel,1,2 and Philip C. Hanawalt2

Institute for Cancer Studies, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom,1 Department of Biological Sciences, Stanford University, Stanford, California2

Received 12 July 2006/ Returned for modification 7 August 2006/ Accepted 18 September 2006

Nucleotide excision repair (NER), which is arguably the most versatile DNA repair system, is strongly attenuated in human cells of the monocytic lineage when they differentiate into macrophages. Within active genes, however, both DNA strands continue to be proficiently repaired. The proficient repair of the nontranscribed strand cannot be explained by the dedicated subpathway of transcription-coupled repair (TCR), which is targeted to the transcribed strand in expressed genes. We now report that the previously termed differentiation-associated repair (DAR) depends upon transcription, but not simply upon RNA polymerase II (RNAPII) encountering a lesion: proficient repair of both DNA strands can occur in a part of a gene that the polymerase never reaches, and even if the translocation of RNAPII is blocked with transcription inhibitors. This suggests that DAR may be a subset of global NER, restricted to the subnuclear compartments or chromatin domains within which transcription occurs. Downregulation of selected NER genes with small interfering RNA has confirmed that DAR relies upon the same genes as global genome repair, rather than upon TCR-specific genes. Our findings support the general view that the genomic domains within which transcription is active are more accessible than the bulk of the genome to the recognition and repair of lesions through the global pathway and that TCR is superimposed upon that pathway of NER.

* Corresponding author. Mailing address: Institute for Cancer Studies, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom. Phone: 44 114 271 2966. Fax: 44 114 271 3892. E-mail: t.nouspikel{at}sheffield.ac.uk.

{triangledown} Published ahead of print on 2 October 2006.

Molecular and Cellular Biology, December 2006, p. 8722-8730, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.01263-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Episkopou, H., Kyrtopoulos, S. A., Sfikakis, P. P., Fousteri, M., Dimopoulos, M. A., Mullenders, L. H.F., Souliotis, V. L. (2009). Association between Transcriptional Activity, Local Chromatin Structure, and the Efficiencies of Both Subpathways of Nucleotide Excision Repair of Melphalan Adducts. Cancer Res. 69: 4424-4433 [Abstract] [Full Text]  
  • Narciso, L., Fortini, P., Pajalunga, D., Franchitto, A., Liu, P., Degan, P., Frechet, M., Demple, B., Crescenzi, M., Dogliotti, E. (2007). Terminally differentiated muscle cells are defective in base excision DNA repair and hypersensitive to oxygen injury. Proc. Natl. Acad. Sci. USA 104: 17010-17015 [Abstract] [Full Text]  
  • Lin, Y., Wilson, J. H. (2007). Transcription-Induced CAG Repeat Contraction in Human Cells Is Mediated in Part by Transcription-Coupled Nucleotide Excision Repair. Mol. Cell. Biol. 27: 6209-6217 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»