Resolution of Sister Centromeres Requires RanBP2-Mediated SUMOylation of Topoisomerase IIα

Meelad M. Dawlaty, Liviu Malureanu, Karthik B. Jeganathan, Esther Kao, Claudio Sustmann, Samuel Tahk, Ke Shuai, Rudolf Grosschedl, Jan M. van Deursen

Research output: Contribution to journalArticlepeer-review

218 Scopus citations

Abstract

RanBP2 is a nucleoporin with SUMO E3 ligase activity that functions in both nucleocytoplasmic transport and mitosis. However, the biological relevance of RanBP2 and the in vivo targets of its E3 ligase activity are unknown. Here we show that animals with low amounts of RanBP2 develop severe aneuploidy in the absence of overt transport defects. The main chromosome segregation defect in cells from these mice is anaphase-bridge formation. Topoisomerase IIα (Topo IIα), which decatenates sister centromeres prior to anaphase onset to prevent bridges, fails to accumulate at inner centromeres when RanBP2 levels are low. We find that RanBP2 sumoylates Topo IIα in mitosis and that this modification is required for its proper localization to inner centromeres. Furthermore, mice with low amounts of RanBP2 are highly sensitive to tumor formation. Together, these data identify RanBP2 as a chromosomal instability gene that regulates Topo IIα by sumoylation and suppresses tumorigenesis.

Original languageEnglish (US)
Pages (from-to)103-115
Number of pages13
JournalCell
Volume133
Issue number1
DOIs
StatePublished - Apr 4 2008
Externally publishedYes

Keywords

  • CELLBIO
  • CELLCYCLE
  • PROTEINS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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