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

Dawlaty, M. M., Malureanu, L., Jeganathan, K. B., Kao, E., Sustmann, C., Tahk, S., et al. (2008). Resolution of Sister Centromeres Requires RanBP2-Mediated SUMOylation of Topoisomerase IIα. Cell, 133, 103-115. doi:10.1016/j.cell.2008.01.045.

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Dawlaty, Meelad M.1, Author
Malureanu, Liviu1, Author
Jeganathan, Karthik B.1, Author
Kao, Esther1, Author
Sustmann, Claudio2, Author              
Tahk, Samuel1, Author
Shuai, K.1, Author
Grosschedl, Rudolf2, Author              
van Deursen, Jan M.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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 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.

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Language(s): eng - English
 Dates: 2008-04-04
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.cell.2008.01.045
 Degree: -

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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 133 Sequence Number: - Start / End Page: 103 - 115 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183