SUMOylation of DNA topoisomerase IIα regulates histone H3 kinase Haspin and H3 phosphorylation in mitosis
| Autor: | Steven P. Gygi, Makoto Michael Yoshida, Lily Ting, Yoshiaki Azuma |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Protein sumoylation Threonine Centromere Mitosis macromolecular substances Protein Serine-Threonine Kinases environment and public health Article Chromosome segregation Histones 03 medical and health sciences Histone H3 Xenopus laevis 0302 clinical medicine Antigens Neoplasm Chromosome Segregation Animals Aurora Kinase B Phosphorylation Kinetochores Chromosome separation Research Articles biology Kinetochore Intracellular Signaling Peptides and Proteins Sumoylation Cell Biology Cell biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) 030104 developmental biology Histone DNA Topoisomerases Type II 030220 oncology & carcinogenesis embryonic structures biology.protein Protein Binding |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Yoshida et al. show that mitotic SUMOylation of TOP2A C-terminal domain promotes its association with phosphorylated Haspin kinase through Haspin’s SUMO-interacting motifs to regulate recruitment of Aurora B kinase at mitotic centromeres. DNA topoisomerase II (TOP2) plays a pivotal role in faithful chromosome separation through its strand-passaging activity that resolves tangled genomic DNA during mitosis. Additionally, TOP2 controls progression of mitosis by activating cell cycle checkpoints. Recent work showed that the enzymatically inert C-terminal domain (CTD) of TOP2 and its posttranslational modification are critical to this checkpoint regulation. However, the molecular mechanism has not yet been determined. By using Xenopus laevis egg extract, we found that SUMOylation of DNA topoisomerase IIα (TOP2A) CTD regulates the localization of the histone H3 kinase Haspin and phosphorylation of histone H3 at threonine 3 at the centromere, two steps known to be involved in the recruitment of the chromosomal passenger complex (CPC) to kinetochores in mitosis. Robust centromeric Haspin localization requires SUMOylated TOP2A CTD binding activity through SUMO-interaction motifs and the phosphorylation of Haspin. We propose a novel mechanism through which the TOP2 CTD regulates the CPC via direct interaction with Haspin at mitotic centromeres. |
| Databáze: | OpenAIRE |
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