- THIS ARTICLE
- Full Text (Rapid PDF)
-
All Versions of this Article:
genetics.105.047167v1
172/2/783 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Takahashi, Y.
- Articles by Strunnikov, A.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Takahashi, Y.
- Articles by Strunnikov, A.
doi:10.1534/genetics.105.047167
A more recent version of this article appeared on February 1, 2006.
REGULAR RESEARCH PAPERS |
SIZ1/SIZ2 control of chromosome transmission fidelity is mediated by the sumoylation of topoisomerase II
Yoshimitsu Takahashi 1, Vladimir Yong-Gonzalez 1, Yoshiko Kikuchi 2 and Alexander Strunnikov 1*
1 NIH, NICHD
2 The University of Tokyo
* To whom correspondence should be addressed. E-mail: strunnik{at}box-s.nih.gov.
Submitted on June 22, 2005
Revised on August 24, 2005
Accepted on 21 September 2005
The Smt3 (SUMO) protein is conjugated to substrate proteins through a cascade of E1, E2 and E3 enzymes. In budding yeast, the E3 step in sumoylation is largely controlled by Siz1p and Siz2p. Analysis of Siz- cells shows that SUMO E3 is required for minichromosome segregation and thus has a positive role in maintaining the fidelity of mitotic transmission of genetic information. Sumoylation of the carboxy-terminus of Top2p, a known SUMO target, is mediated by Siz1p and Siz2p both in vivo and in vitro. Sumoylation in vitro reveals that Top2p is an extremely potent substrate for Smt3p conjugation and that chromatin-bound Top2p can still be sumoylated, unlike many other SUMO substrates. By combining mutations in the TOP2 sumoylation sites and the SIZ1 and SIZ2 genes we demonstrate that the minichromosome segregation defect and dicentric minichromosome stabilization, both characteristic for Smt3p-E3-deficient cells, are mediated by the lack of Top2p sumoylation in these cells. A role for Smt3p-modification as a signal for Top2p targeting to pericentromeric regions was suggested by an analysis of Top2p-Smt3p fusion. We propose a model for the positive control of the centromeric pool of Top2p, required for high segregation fidelity, by Smt3p modification.
Key Words: SUMO, Smt3, centromere, chromosome segregation, topoisomerase II
This article has been cited by other articles:
 |
|
 |
|
  L. A. Diaz-Martinez, J. F. Gimenez-Abian, and D. J. Clarke Chromosome cohesion - rings, knots, orcs and fellowship J. Cell Sci., July 1, 2008; 121(13): 2107 - 2114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Agostinho, V. Santos, F. Ferreira, R. Costa, J. Cardoso, I. Pinheiro, J. Rino, E. Jaffray, R. T. Hay, and J. Ferreira Conjugation of Human Topoisomerase 2{alpha} with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity Cancer Res., April 1, 2008; 68(7): 2409 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Spence, H. H. Phua, W. Mills, A. J. Carpenter, A. C. G. Porter, and C. J. Farr Depletion of topoisomerase II{alpha} leads to shortening of the metaphase interkinetochore distance and abnormal persistence of PICH-coated anaphase threads J. Cell Sci., November 15, 2007; 120(22): 3952 - 3964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-Y. Huang, D. Kowalski, H. Minderman, N. Gandhi, and E. S. Johnson Small Ubiquitin-Related Modifier Pathway Is a Major Determinant of Doxorubicin Cytotoxicity in Saccharomyces cerevisiae Cancer Res., January 15, 2007; 67(2): 765 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Egydio de Carvalho and M. P. Colaiacovo SUMO-mediated regulation of synaptonemal complex formation during meiosis Genes & Dev., August 1, 2006; 20(15): 1986 - 1992. [Full Text] [PDF]
|
|