The topoisomerase IIβ circular clamp arrests transcription and signals a 26S proteasome pathway

Hai Xiao, Yong Mao, Shyamal D. Desai, Nai Zhou, Chun Yuan Ting, Jaulang Hwang, Leroy-Fong Liu

研究成果: 雜誌貢獻文章同行評審

70 引文 斯高帕斯(Scopus)

摘要

It has been proposed that the topoisomerase II (TOP2)β-DNA covalent complex arrests transcription and triggers 26S proteasome-mediated degradation of TOP2β. It is unclear whether the initial trigger for proteasomal degradation is due to DNA damage or transcriptional arrest. In the current study we show that the TOP2 catalytic inhibitor 4,4-(2,3-butanediyl)-bis(2,6-piperazinedione) (ICRF-193), which traps TOP2 into a circular clamp rather than the TOP2-DNA covalent complex, can also arrest transcription. Arrest of transcription, which is TOP2β-dependent, is accompanied by proteasomal degradation of TOP2β. Different from TOP2 poisons and other DNA-damaging agents, ICRF-193 did not induce proteasomal degradation of the large subunit of RNA polymerase II. These results suggest that proteasomal degradation of TOP2β induced by the TOP2-DNA covalent complex or the TOP2 circular clamp is due to transcriptional arrest but not DNA damage. By contrast, degradation of the large subunit of RNA polymerase II is due to a DNA-damage signal.

原文英語
頁(從 - 到)3239-3244
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
100
發行號6
DOIs
出版狀態已發佈 - 三月 18 2003
對外發佈

ASJC Scopus subject areas

  • 遺傳學
  • 多學科

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