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 F. Liu

Research output: Contribution to journalArticle

105 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 (US)
Pages (from-to)2341-2350
Number of pages10
JournalMolecular and cellular biology
Volume23
Issue number7
DOIs
StatePublished - Apr 1 2003

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Type I DNA Topoisomerase
RNA
RNA Polymerase II
DNA-Directed RNA Polymerases
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Desai, S. D., Zhang, H., Rodriguez-Bauman, A., Yang, J-M., Wu, X., Gounder, M. K., ... 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
Desai, Shyamal D. ; Zhang, Hui ; Rodriguez-Bauman, Alexandra ; Yang, Jin-Ming ; Wu, Xiaohua ; Gounder, Murugesan K. ; Rubin, Eric H. ; Liu, Leroy F. / Transcription-dependent degradation of topoisomerase I-DNA covalent complexes. In: Molecular and cellular biology. 2003 ; Vol. 23, No. 7. pp. 2341-2350.
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Desai, SD, Zhang, H, Rodriguez-Bauman, A, Yang, J-M, Wu, X, Gounder, MK, Rubin, EH & Liu, LF 2003, 'Transcription-dependent degradation of topoisomerase I-DNA covalent complexes', Molecular and cellular biology, vol. 23, no. 7, pp. 2341-2350. https://doi.org/10.1128/MCB.23.7.2341-2350.2003

Transcription-dependent degradation of topoisomerase I-DNA covalent complexes. / Desai, Shyamal D.; Zhang, Hui; Rodriguez-Bauman, Alexandra; Yang, Jin-Ming; Wu, Xiaohua; Gounder, Murugesan K.; Rubin, Eric H.; Liu, Leroy F.

In: Molecular and cellular biology, Vol. 23, No. 7, 01.04.2003, p. 2341-2350.

Research output: Contribution to journalArticle

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Desai SD, Zhang H, Rodriguez-Bauman A, Yang J-M, Wu X, Gounder MK et al. Transcription-dependent degradation of topoisomerase I-DNA covalent complexes. Molecular and cellular biology. 2003 Apr 1;23(7):2341-2350. https://doi.org/10.1128/MCB.23.7.2341-2350.2003