Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.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.
Agostinho,
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.
2008, Pubmed,
Xenbase
Agostinho,
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.
2008,
Pubmed
,
Xenbase
Arnaoutov,
The Ran GTPase regulates kinetochore function.
2003,
Pubmed
,
Xenbase
Azuma,
SUMO-2/3 regulates topoisomerase II in mitosis.
2003,
Pubmed
,
Xenbase
Azuma,
PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes.
2005,
Pubmed
,
Xenbase
Azuma,
Analysis of SUMOylation of topoisomerase IIalpha with Xenopus egg extracts.
2009,
Pubmed
,
Xenbase
Bachant,
The SUMO-1 isopeptidase Smt4 is linked to centromeric cohesion through SUMO-1 modification of DNA topoisomerase II.
2002,
Pubmed
Chini,
Human claspin is required for replication checkpoint control.
2003,
Pubmed
,
Xenbase
Clarke,
Topoisomerase II inhibition prevents anaphase chromatid segregation in mammalian cells independently of the generation of DNA strand breaks.
1993,
Pubmed
Clarke,
Novel kinetochore function of Topoisomerase IIα.
2015,
Pubmed
,
Xenbase
Coelho,
Dual role of topoisomerase II in centromere resolution and aurora B activity.
2008,
Pubmed
Dasso,
RCC1, a regulator of mitosis, is essential for DNA replication.
1992,
Pubmed
,
Xenbase
Dawlaty,
Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha.
2008,
Pubmed
Dickey,
Impact of the C-terminal domain of topoisomerase IIalpha on the DNA cleavage activity of the human enzyme.
2005,
Pubmed
Downes,
Inhibitors of DNA topoisomerase II prevent chromatid separation in mammalian cells but do not prevent exit from mitosis.
1991,
Pubmed
Errico,
Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts.
2007,
Pubmed
,
Xenbase
Furniss,
Direct monitoring of the strand passage reaction of DNA topoisomerase II triggers checkpoint activation.
2013,
Pubmed
Gareau,
The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.
2010,
Pubmed
Hecker,
Specification of SUMO1- and SUMO2-interacting motifs.
2006,
Pubmed
Heun,
SUMOrganization of the nucleus.
2007,
Pubmed
Kornbluth,
Analysis of the cell cycle using Xenopus egg extracts.
2006,
Pubmed
,
Xenbase
Kumagai,
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Kumagai,
Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1.
2003,
Pubmed
,
Xenbase
Lee,
Roles of replication fork-interacting and Chk1-activating domains from Claspin in a DNA replication checkpoint response.
2005,
Pubmed
,
Xenbase
Lou,
Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint.
2008,
Pubmed
Mao,
SUMO-1 conjugation to human DNA topoisomerase II isozymes.
2000,
Pubmed
Matunis,
SUMO: the glue that binds.
2006,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Nitiss,
DNA topoisomerase II and its growing repertoire of biological functions.
2009,
Pubmed
Petsalaki,
Chk1 and Mps1 jointly regulate correction of merotelic kinetochore attachments.
2013,
Pubmed
Petsalaki,
Phosphorylation at serine 331 is required for Aurora B activation.
2011,
Pubmed
Porter,
Topoisomerase II: untangling its contribution at the centromere.
2004,
Pubmed
Ren,
Systematic study of protein sumoylation: Development of a site-specific predictor of SUMOsp 2.0.
2009,
Pubmed
Reverter,
Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.
2006,
Pubmed
Ryu,
PIASy-dependent SUMOylation regulates DNA topoisomerase IIalpha activity.
2010,
Pubmed
,
Xenbase
Ryu,
PIASy mediates SUMO-2/3 conjugation of poly(ADP-ribose) polymerase 1 (PARP1) on mitotic chromosomes.
2010,
Pubmed
,
Xenbase
Ryu,
Rod/Zw10 complex is required for PIASy-dependent centromeric SUMOylation.
2010,
Pubmed
,
Xenbase
Shamu,
Sister chromatid separation in frog egg extracts requires DNA topoisomerase II activity during anaphase.
1992,
Pubmed
,
Xenbase
Song,
Identification of a SUMO-binding motif that recognizes SUMO-modified proteins.
2004,
Pubmed
Sridharan,
SUMOylation regulates polo-like kinase 1-interacting checkpoint helicase (PICH) during mitosis.
2015,
Pubmed
,
Xenbase
Sudharsan,
The SUMO ligase PIAS1 regulates UV-induced apoptosis by recruiting Daxx to SUMOylated foci.
2012,
Pubmed
Takahashi,
SIZ1/SIZ2 control of chromosome transmission fidelity is mediated by the sumoylation of topoisomerase II.
2006,
Pubmed
Wang,
Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation.
2008,
Pubmed
Zhang,
SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis.
2008,
Pubmed
,
Xenbase
