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

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3239-3244
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number6
DOIs
Publication statusPublished - Mar 18 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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