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Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts.
J Biol Chem. 2004 Apr 30; 279(18):18511-20.JB

Abstract

Transcription and repair of many DNA helix-distorting lesions such as cyclobutane pyrimidine dimers have been shown to be coupled in cells across phyla from bacteria to humans. The signal for transcription-coupled repair appears to be a stalled transcription complex at the lesion site. To determine whether oxidative DNA lesions can block correctly initiated human RNA polymerase II, we examined the effect of site-specifically introduced oxidative damages on transcription in HeLa cell nuclear extracts. We found that transcription was blocked by single-stranded breaks, common oxidative DNA lesions, when present in the transcribed strand of the transcription template. Cyclobutane pyrimidine dimers, which have been previously shown to block transcription both in vitro and in vivo, also blocked transcription in the HeLa cell nuclear transcription assay. In contrast, the oxidative DNA base lesions, 8-oxoguanine, 5-hydroxycytosine, and thymine glycol did not inhibit transcription, although pausing was observed with the thymine glycol lesion. Thus, DNA strand breaks but not oxidative DNA base damages blocked transcription by RNA polymerase II.

Authors+Show Affiliations

Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont 05405-0068, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14978042

Citation

Kathe, Scott D., et al. "Single-stranded Breaks in DNA but Not Oxidative DNA Base Damages Block Transcriptional Elongation By RNA Polymerase II in HeLa Cell Nuclear Extracts." The Journal of Biological Chemistry, vol. 279, no. 18, 2004, pp. 18511-20.
Kathe SD, Shen GP, Wallace SS. Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts. J Biol Chem. 2004;279(18):18511-20.
Kathe, S. D., Shen, G. P., & Wallace, S. S. (2004). Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts. The Journal of Biological Chemistry, 279(18), 18511-20.
Kathe SD, Shen GP, Wallace SS. Single-stranded Breaks in DNA but Not Oxidative DNA Base Damages Block Transcriptional Elongation By RNA Polymerase II in HeLa Cell Nuclear Extracts. J Biol Chem. 2004 Apr 30;279(18):18511-20. PubMed PMID: 14978042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts. AU - Kathe,Scott D, AU - Shen,Guang-Ping, AU - Wallace,Susan S, Y1 - 2004/02/21/ PY - 2004/2/24/pubmed PY - 2004/6/21/medline PY - 2004/2/24/entrez SP - 18511 EP - 20 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 279 IS - 18 N2 - Transcription and repair of many DNA helix-distorting lesions such as cyclobutane pyrimidine dimers have been shown to be coupled in cells across phyla from bacteria to humans. The signal for transcription-coupled repair appears to be a stalled transcription complex at the lesion site. To determine whether oxidative DNA lesions can block correctly initiated human RNA polymerase II, we examined the effect of site-specifically introduced oxidative damages on transcription in HeLa cell nuclear extracts. We found that transcription was blocked by single-stranded breaks, common oxidative DNA lesions, when present in the transcribed strand of the transcription template. Cyclobutane pyrimidine dimers, which have been previously shown to block transcription both in vitro and in vivo, also blocked transcription in the HeLa cell nuclear transcription assay. In contrast, the oxidative DNA base lesions, 8-oxoguanine, 5-hydroxycytosine, and thymine glycol did not inhibit transcription, although pausing was observed with the thymine glycol lesion. Thus, DNA strand breaks but not oxidative DNA base damages blocked transcription by RNA polymerase II. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/14978042/Single_stranded_breaks_in_DNA_but_not_oxidative_DNA_base_damages_block_transcriptional_elongation_by_RNA_polymerase_II_in_HeLa_cell_nuclear_extracts_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=14978042 DB - PRIME DP - Unbound Medicine ER -