Transcription-dependent degradation of topoisomerase I-DNA covalent complexes

Shyamal D. Desai, Hui Zhang, Alexandra Rodriguez-Bauman, Jin Ming Yang, Xiaohua Wu, Murugesan K. Gounder, Eric H. Rubin, Leroy-Fong Liu

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Topoisomerase I (Top I)-DNA covalent complexes represent a unique type of DNA lesion whose repair and processing remain unclear. In this study, we show that Top I-DNA covalent complexes transiently arrest RNA transcription in normal nontransformed cells. Arrest of RNA transcription is coupled to activation of proteasomal degradation of Top I and the large subunit of RNA polymerase II. Recovery of transcription occurs gradually and depends on both proteasomal degradation of Top I and functional transcription-coupled repair (TCR). These results suggest that arrest of the RNA polymerase elongation complex by the Top I-DNA covalent complex triggers a 26S proteasome-mediated signaling pathway(s) leading to degradation of both Top I and the large subunit of RNA polymerase II. We propose that proteasomal degradation of Top I and RNA polymerase II precedes repair of the exposed single-strand breaks by TCR.

Original languageEnglish
Pages (from-to)2341-2350
Number of pages10
JournalMolecular and Cellular Biology
Volume23
Issue number7
DOIs
Publication statusPublished - Apr 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Desai, S. D., Zhang, H., Rodriguez-Bauman, A., Yang, J. M., Wu, X., Gounder, M. K., Rubin, E. H., & Liu, L-F. (2003). Transcription-dependent degradation of topoisomerase I-DNA covalent complexes. Molecular and Cellular Biology, 23(7), 2341-2350. https://doi.org/10.1128/MCB.23.7.2341-2350.2003