SUMO-1 conjugation to human DNA topoisomerase II isozymes

Yong Mao, Shyamal D. Desai, Leroy-Fong Liu

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Topoisomerase I-mediated DNA damage induced by camptothecin has been shown to induce rapid small ubiquitin-related modifier (SUMO)-1 conjugation to topoisomerase I. In the current study, we show that topoisomerase II-mediated DNA damage induced by teniposide (VM-26) results in the formation of high molecular weight conjugates of both topoisomerase IIα and IIβ isozymes in HeLa cells. Immunological characterization of these conjugates suggests that both topoisomerase IIα and IIβ isozymes are conjugated to SUMO-1. The involvement of SUMO-1/UBC9 in the modification of topoisomerase II isozymes is also supported by the demonstration of physical interaction between topoisomerase II and SUMO-1/UBC9. Surprisingly, ICRF-193, which does not induce topoisomerase II-mediated DNA damage but traps topoisomerase II into a circular clamp conformation, is also shown to induce similar SUMO-1 conjugation to topoisomerase II isozymes. In addition, we show that both oxidative and heat shock stresses, which can cause protein damage, rapidly increase nuclear SUMO-1 conjugates. These studies raise the question on whether SUMO-1 conjugation to topoisomerases is an indirect result of a DNA damage response or a direct result because of protein conformational changes.

Original languageEnglish
Pages (from-to)26066-26073
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number34
DOIs
Publication statusPublished - Aug 25 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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