Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha.
Cell
; 133(1): 103-15, 2008 Apr 04.
Article
em En
| MEDLINE
| ID: mdl-18394993
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Centrômero
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DNA Topoisomerases Tipo II
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Chaperonas Moleculares
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Complexo de Proteínas Formadoras de Poros Nucleares
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Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina
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Proteínas de Ligação a DNA
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Antígenos de Neoplasias
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article