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SUMOylation of the C-terminal domain of DNA topoisomerase IIα regulates the centromeric localization of Claspin

Ryu, Hyunju and Yoshida, Makoto M. and Sridharan, Vinidhra and Kumagai, Akiko and Dunphy, William G. and Dasso, Mary and Azuma, Yoshiaki (2015) SUMOylation of the C-terminal domain of DNA topoisomerase IIα regulates the centromeric localization of Claspin. Cell Cycle, 14 (17). pp. 2777-2784. ISSN 1538-4101. https://resolver.caltech.edu/CaltechAUTHORS:20150924-153316094

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Abstract

DNA topoisomerase II (TopoII) regulates DNA topology by its strand passaging reaction, which is required for genome maintenance by resolving tangled genomic DNA. In addition, TopoII contributes to the structural integrity of mitotic chromosomes and to the activation of cell cycle checkpoints in mitosis. Post-translational modification of TopoII is one of the key mechanisms by which its broad functions are regulated during mitosis. SUMOylation of TopoII is conserved in eukaryotes and plays a critical role in chromosome segregation. Using Xenopus laevis egg extract, we demonstrated previously that TopoIIα is modified by SUMO on mitotic chromosomes and that its activity is modulated via SUMOylation of its lysine at 660. However, both biochemical and genetic analyses indicated that TopoII has multiple SUMOylation sites in addition to Lys660, and the functions of the other SUMOylation sites were not clearly determined. In this study, we identified the SUMOylation sites on the C-terminal domain (CTD) of TopoIIα. CTD SUMOylation did not affect TopoIIα activity, indicating that its function is distinct from that of Lys660 SUMOylation. We found that CTD SUMOylation promotes protein binding and that Claspin, a well-established cell cycle checkpoint mediator, is one of the SUMOylation-dependent binding proteins. Claspin harbors 2 SUMO-interacting motifs (SIMs), and its robust association to mitotic chromosomes requires both the SIMs and TopoIIα-CTD SUMOylation. Claspin localizes to the mitotic centromeres depending on mitotic SUMOylation, suggesting that TopoIIα-CTD SUMOylation regulates the centromeric localization of Claspin. Our findings provide a novel mechanistic insight regarding how TopoIIα-CTD SUMOylation contributes to mitotic centromere activity.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1080/15384101.2015.1066537DOIArticle
http://www.tandfonline.com/doi/full/10.1080/15384101.2015.1066537PublisherArticle
ORCID:
AuthorORCID
Kumagai, Akiko0000-0003-2422-8053
Dunphy, William G.0000-0001-7598-8939
Additional Information:© 2015 Taylor & Francis Group, LLC. Received: 29 Apr 2015; Accepted: 23 Jun 2015; Accepted author version posted online: 01 Jul 2015; Published online: 01 Jul 2015. We thank for D. Clarke and H. Funabiki for their critical discussion of this project. We thank NPG Language editing for editorial assistance. This project was supported by NIH/NIGMS, GM80278 and by bridge funding from the University of Kansas. W.G. Dunphy and A. Kumagai are supported by NIH/NIGMS (GM043974 and GM070891). M. Dasso is supported by NICHD (project no. HD001902). No potential conflicts of interest were disclosed.
Funders:
Funding AgencyGrant Number
NIHGM80278
University of KansasUNSPECIFIED
NIHGM043974
NIHGM070891
NIHHD001902
Issue or Number:17
Record Number:CaltechAUTHORS:20150924-153316094
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150924-153316094
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:60498
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Sep 2015 23:40
Last Modified:09 Mar 2020 13:18

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