Resolution of Sister Centromeres Requires RanBP2-mediated SUMOylation of Topoisomerase IIalpha

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2008 Apr 9

PMID 18394993

Citations 178

Authors

Meelad M Dawlaty

Liviu Malureanu

Karthik B Jeganathan

Esther Kao

Claudio Sustmann

Samuel Tahk

Ke Shuai

Rudolf Grosschedl

Jan M van Deursen

Affiliations

Soon will be listed here.

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 IIalpha (Topo IIalpha), 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 IIalpha 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 IIalpha by sumoylation and suppresses tumorigenesis.

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