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 language | English |
|---|---|
| Pages (from-to) | 2341-2350 |
| Number of pages | 10 |
| Journal | Molecular and Cellular Biology |
| Volume | 23 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Apr 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology
Cite this
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-Fong.
In: Molecular and Cellular Biology, Vol. 23, No. 7, 04.2003, p. 2341-2350.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transcription-dependent degradation of topoisomerase I-DNA covalent complexes
AU - Desai, Shyamal D.
AU - Zhang, Hui
AU - Rodriguez-Bauman, Alexandra
AU - Yang, Jin Ming
AU - Wu, Xiaohua
AU - Gounder, Murugesan K.
AU - Rubin, Eric H.
AU - Liu, Leroy-Fong
PY - 2003/4
Y1 - 2003/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037378557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037378557&partnerID=8YFLogxK
U2 - 10.1128/MCB.23.7.2341-2350.2003
DO - 10.1128/MCB.23.7.2341-2350.2003
M3 - Article
C2 - 12640119
AN - SCOPUS:0037378557
VL - 23
SP - 2341
EP - 2350
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 7
ER -