PIASy-dependent SUMOylation regulates DNA topoisomerase IIα activity
dc.contributor.author | Ryu, Hyunju | |
dc.contributor.author | Furuta, Maiko | |
dc.contributor.author | Kirkpatrick, Donald | |
dc.contributor.author | Gygi, Steven P. | |
dc.contributor.author | Azuma, Yoshiaki | |
dc.date.accessioned | 2014-04-15T18:36:59Z | |
dc.date.available | 2014-04-15T18:36:59Z | |
dc.date.issued | 2010-11-15 | |
dc.identifier.citation | Ryu, Hyunju, Maiko Furuta, Donald Kirkpatrick, Steven P. Gygi, and Yoshiaki Azuma. 2010. “PIASy-dependent SUMOylation regulates DNA topoisomerase IIα activity.” J Cell Biol 191:783-794. http://dx.doi.org/10.1083/jcb.201004033 | |
dc.identifier.uri | http://hdl.handle.net/1808/13490 | |
dc.description.abstract | DNA topoisomerase IIα (TopoIIα) is an essential chromosome-associated enzyme with activity implicated in the resolution of tangled DNA at centromeres before anaphase onset. However, the regulatory mechanism of TopoIIα activity is not understood. Here, we show that PIASy-mediated small ubiquitin-like modifier 2/3 (SUMO2/3) modification of TopoIIα strongly inhibits TopoIIα decatenation activity. Using mass spectrometry and biochemical analysis, we demonstrate that TopoIIα is SUMOylated at lysine 660 (Lys660), a residue located in the DNA gate domain, where both DNA cleavage and religation take place. Remarkably, loss of SUMOylation on Lys660 eliminates SUMOylation-dependent inhibition of TopoIIα, which indicates that Lys660 SUMOylation is critical for PIASy-mediated inhibition of TopoIIα activity. Together, our findings provide evidence for the regulation of TopoIIα activity on mitotic chromosomes by SUMOylation. Therefore, we propose a novel mechanism for regulation of centromeric DNA catenation during mitosis by PIASy-mediated SUMOylation of TopoIIα. | |
dc.description.sponsorship | M. Furuta was supported as a Japan Society for the Promotion of Science Research Fellow in Biomedical and Behavioral Research at the National Institutes of Health. This project was supported in part by a start-up grant from the Department of Molecular Biosciences at the University of Kansas and National Institutes of Health/National Center for Research Resources, Center For Cancer Experimental Therapeutics at the Centers of Biomedical Research Excellence (CCET-COBRE; P20 RR015563), and is currently supported by National Institutes of Health/National Institute of General Medical Sciences grants GM80278 and GM67945 (to S.P. Gygi). | |
dc.publisher | The Rockerfeller University Press | |
dc.rights | This article is distributed under the terms of an Attribution Noncommercial Share Alike No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution Noncommercial Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | |
dc.title | PIASy-dependent SUMOylation regulates DNA topoisomerase IIα activity | |
dc.type | Article | |
kusw.kuauthor | Ryu, Hyunju | |
kusw.kuauthor | Furuta, Maiko | |
kusw.kuauthor | Azuma, Yoshiaki | |
kusw.kudepartment | Department of Molecular Biosciences | |
kusw.oastatus | fullparticipation | |
dc.identifier.doi | 10.1083/jcb.201004033 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This article is distributed under the terms of an Attribution Noncommercial Share Alike No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution Noncommercial Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).