- MB Director of Graduate Studies
The role of posttranslational modification by SUMO on cell division cycle.
Posttranslational protein modification modulates the biochemical and cell biological function of the proteins and has essential role to regulate various physiological phenomena. SUMO family of protein is small ubiquitin-related protein that modifies various cellular proteins to be conjugated to substrates in a manner similar to Ubiquitin (SUMO modification). Genetic analysis indicates that SUMO modification is essential for viability in eukaryote. Defect in SUMO modification caused aberrant mitosis in yeast and fruit fly, suggesting the SUMO modification pathway is involved in proper progression of mitosis. I have found that mitotic specific SUMO modification has crucial role in chromosome segregation by using Xenopus egg extracts in vitro cell cycle assay system. My lab will focus on understanding a role of mitotic SUMO modification in respect to chromosome segregation, especially, the function of SUMO modification on DNA topoisomerase II (TopoII), which is a major SUMO modified substrate in mitosis. During mitosis, chromosomes dramatically change their structure to organize proper structure for mitotic chromosome. This event is essential to separate sister chromosomes faithfully in anaphase of mitosis. TopoII is one of the key enzymes to organize proper chromosome structure, thus SUMO modification of TopoII suggested to have important role of regulation of chromosomal structure during mitosis. My lab will utilize Xenopus egg extracts in vitro cell cycle assay to study biochemical and cell biological function of mitotic SUMO modification.
- Cell biology
- Cell cycle
Selected Publications —
Clarke, D J, and Y Azuma. “Non-Catalytic Roles of the Topoisomerase IIα C-Terminal Domain.” Journal Articles. International Journal of Molecular Sciences 18, no. 11 (October 17, 2017). .
Kaur, K, H Park, N Pandey, Y Azuma, and R N De Guzman. “Identification of a New Small Ubiquitin-like Modifier (SUMO)-Interacting Motif in the E3 Ligase PIASy.” Journal Articles. The Journal of Biological Chemistry 292, no. 24 (May 16, 2017): 10230–38. .
Yoshida, Makoto M, and Yoshiaki Azuma. “Mechanisms behind Topoisomerase II SUMOylation in Chromosome Segregation.” Journal Articles. Cell Cycle, July 2, 2016.
Yoshida, Makoto M, Lily Ting, Steven P Gygi, and Yoshiaki Azuma. “SUMOylation of DNA Topoisomerase IIα Regulates Histone H3 Kinase Haspin and H3 Phosphorylation in Mitosis.” Journal Articles. Journal of Cell Biology 213, no. 6 (May 20, 2016): 665–78.
Sridharan, Vinidhra, and Yoshiaki Azuma. “SUMO-Interacting Motifs (SIMs) in Polo-like Kinase 1-Interacting Checkpoint Helicase (PICH) Ensure Proper Chromosome Segregation during Mitosis.” Journal Articles. Cell Cycle, 26, 2016.
Ryu, Hyunju, Makoto M Yoshida, Vinidhra Sridharan, Akiko Kumagai, William G Dunphy, Mary Dasso, and Yoshiaki Azuma. “SUMOylation of the C-Terminal Domain of DNA Topoisomerase IIα Regulates the Centromeric Localization of Claspin.” Journal Articles. Cell Cycle, June 1, 2015.
Sridharan, Vinidhra, Hyewon Park, Hyunju Ryu, and Yoshiaki Azuma. “SUMOylation Regulates Polo-like Kinase 1-Interacting Checkpoint Helicase (PICH) during Mitosis.” Journal Articles. The Journal of Biological Chemistry, February 2015.
Sudharsan, R., and Y. Azuma. “The SUMO Ligase PIAS1 Regulates UV-Induced Apoptosis by Recruiting Daxx to SUMOylated Foci.” Journal Articles. J Cell Sci 125 (2012): 5819–29.
Ryu, H., G. Al-Ani, K. Deckert, D. Kirkpatrick, S. P. Gygi, M. Dasso, and Y. Azuma. “PIASy Mediates SUMO-2/3 Conjugation of Poly (ADP-Ribose) Polymerase1 (PARP1) on Mitotic Chromosomes.” Journal Articles. J Biol Chem 285 (2010): 14415–23.
Ryu, H., M. Furuta, D. Kirkpatrick, S. P. Gygi, and Y. Azuma. “PIASy-Dependent SUMOylation Regulates DNA Topoisomerase IIα Activity.” Journal Articles. J Cell Biol 191 (2010): 783–94.
Creative Works —
Hassebroek, V.A., Park, H., Pandey, N., Lerbakken, B.T., Aksenova, V., Arnaoutov, A., Dasso, M., and Azuma, Y. (2020). PICH regulates the abundance and localization of SUMOylated proteins on mitotic chromosomes. Mol Biol Cell 31, 2537-2556.
Pandey, N., Keifenheim, D., Yoshida, M.M., Hassebroek, V.A., Soroka, C., Azuma, Y., and Clarke, D.J. (2020). Topoisomerase II SUMOylation activates a metaphase checkpoint via Haspin and Aurora B kinases. J Cell Biol 219.
Yoshida, M.M., Ting, L., Gygi, S.P., and Azuma, Y. (2016). SUMOylation of DNA topoisomerase IIalpha regulates histone H3 kinase Haspin and H3 phosphorylation in mitosis. J Cell Biol 213, 665-678.
Sridharan, V., and Azuma, Y. (2016). SUMO-interacting motifs (SIMs) in Polo-like kinase 1-interacting checkpoint helicase (PICH) ensure proper chromosome segregation during mitosis. Cell Cycle 15, 2135-2144.
Sridharan, V., Park, H., Ryu, H., and Azuma, Y. (2015). SUMOylation regulates polo-like kinase 1-interacting checkpoint helicase (PICH) during mitosis. J Biol Chem 290, 3269-3276.
Ryu, H., Yoshida, M.M., Sridharan, V., Kumagai, A., Dunphy, W.G., Dasso, M., and Azuma, Y. (2015). SUMOylation of the C-terminal domain of DNA topoisomerase IIalpha regulates the centromeric localization of Claspin. Cell Cycle 14, 2777-2784.
Sudharsan, R., and Azuma, Y. (2012). The SUMO ligase PIAS1 regulates UV-induced apoptosis by recruiting Daxx to SUMOylated foci. J Cell Sci 125, 5819-5829.
Ryu, H., Furuta, M., Kirkpatrick, D., Gygi, S.P., and Azuma, Y. (2010). PIASy-dependent SUMOylation regulates DNA topoisomerase IIalpha activity. J Cell Biol 191, 783-794.
Ryu, H., and Azuma, Y. (2010). Rod/Zw10 complex is required for PIASy-dependent centromeric SUMOylation. J Biol Chem 285, 32576-32585.
Ryu, H., Al-Ani, G., Deckert, K., Kirkpatrick, D., Gygi, S.P., Dasso, M., and Azuma, Y. (2010). PIASy mediates SUMO-2/3 conjugation of poly(ADP-ribose) polymerase 1 (PARP1) on mitotic chromosomes. J Biol Chem 285, 14415-14423.
Azuma, Y., Arnaoutov, A., Anan, T., and Dasso, M. (2005). PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes. EMBO J 24, 2172-2182.
Azuma, Y., Arnaoutov, A., and Dasso, M. (2003). SUMO-2/3 regulates topoisomerase II in mitosis. J Cell Biol 163, 477-487.