Biomolecular Networks Laboratories

Laboratory of Chromosome Biology

Prof. FUKAGAWA Tatsuo Prof. FUKAGAWA Tatsuo


Chromosome, Kinetochore, Centromere, Chromosome segregation

How are chromosomes segregated into daughter cells?

The kinetochore plays a fundamental role in accurate chromosome segregation during mitosis and meiosis in eukaryotes. Although chromosome segregation errors cause genetic diseases, including some cancers, the mechanisms of how kinetochores interact with microtubules of the spindle apparatus during cell division are not fully understood. To understand the molecular mechanisms of chromosome segregation, we are focusing on the kinetochore and are trying to address how the kinetochore is specified and assembled on centromere chromatin. In addition, we are analyzing how the kinetochore correctly attaches to microtubules. We are utilizing molecular biology, cell biology, biochemistry, structural biology, and genome engineering to clarify kinetochore structure and function.

Molecular model of the kinetochore structure. We would like to address what the structure is and how the structure is established and functions.


FUKAGAWA Tatsuo (Professor) tfukagawa[at]
HORI Tetsuya (Associate Professor) thori[at]
HARA Masatoshi (Assistant Professor) mahara[at]
ARIYOSHI Mariko (Specially Appointed Assistant Professor) mariyoshi[at]
SRIDHAR Shreyas (Specially Appointed Assistant Professor)  
MAKINO Fumiaki (Visiting Researcher)  
TAKESHITA Yumiko (Technical Staff)  
OHSHIMO Kaori (Technical Staff)  
FUKUOKA Reika (Technical Staff)  
KONDO Kyoko (Secretary)  

You could probably reach more information of individual researchers by Research Map and researcher's search of Osaka-U.

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What is your hot research topic?
We are focusing on the question "how is the kinetochore structure is organized?" Since identification of most kinetochore components, many groups are trying to address this question using in vitro reconstitution with recombinant components. However, the kinetochore structure is dynamically changed during progression of the cell cycle, and we would like to clarify how such dynamic changes occur.
What is your breakthrough or research progress in the last 5 years?
The most important role for the kinetochore is to bridge a connection between chromatin and spindle microtubules. Therefore, it is critical to clarify how microtubule binding proteins are recruited into the kinetochore. While many groups proposed that CENP-C is critical for the recruitment of microtubule binding proteins into the kinetochores, we demonstrated that CENP-T is much more critical for this event. This research result broke the mold. Furthermore, we revealed how CENP-C associates with chromatin, based on structure analyses.
What kind of background do your lab members have?
Lab members have backgrounds in science, agriculture, medicine or pharmaceutical sciences. As various techniques are needed to conduct centromere/kinetochore research, we are seeking people from various fields.
Do you collaborate with other institutions and universities?
We are collaborating with scientists from the University of Tokyo, Tokyo tech., the National Institute of Genetics, MIT, the University of Edinburgh, and the Curie Institute.
What kind of careers do your Lab's alumni go on to?
Many of them get research jobs in academia and the business sector. However, some people also work in non-scientific fields.
How do you develop your research?
We mainly used cultured-cells for our centromere/kinetochore studies. However, we would like to study on various mechanisms for chromosomes segregation in organismal context in the future.

Research Highlights

Publications (Research Articles, Reviews, Books)


Mariko Ariyoshi, Fumiaki Makino, Reito Watanabe, Reiko Nakagawa, Takayuki Kato, Keiichi Namba, Yasuhiro Arimura, Risa Fujita, Hitoshi Kurumizaka, Ei-ichi Okumura, Masatoshi Hara, Tatsuo Fukagawa

Cryo-EM structure of the CENP-A nucleosome in complex with phosphorylated CENP-C

EMBO J. 40(5):e105671.  2021 PMID:33463726 DOI:10.15252/embj.2020105671


Kohei Nishimura, Ryotaro Yamada, Shinya Hagihara, Rie Iwasaki, Naoyuki Uchida, Takumi Kamura, Koji Takahashi, Keiko U. Torii, Tatsuo Fukagawa

A super-sensitive auxin-inducible degron system with an engineered auxin-TIR1 pair.

Nucl. Acids. Res. 48(18):e108.  2020 PMID:32941625 DOI:10.1093/nar/gkaa748

Nuno M. C. Martins, Fernanda Cisneros-Soberanis, Elisa Pesenti, Natalia Y. Kochanova1, Wei-Hao Shang, Tetsuya Hori, Takahiro Nagase, Hiroshi Kimura, Vladimir Larionov, Hiroshi Masumoto, Tatsuo Fukagawa, William C. Earnshaw

H3K9me3 Maintenance on a Human Artificial Chromosome Is Required for Segregation but Not Centromere Epigenetic Memory.

J. Cell Sci. 133(14):jcs242610.  2020 PMID:32576667 DOI:10.1242/jcs.242610

Megumi Saito, Naoko Kagawa, Kazuhiro Okumura, Haruka Munakata, Eriko Isogai, Tatsuo Fukagawa, Yuichi Wakabayashi

CENP-50 Is Required for Papilloma Development in the Two-Stage Skin Carcinogenesis Model.

Cancer Sci. 111(8):2850-60  2020 PMID:32535988 DOI:10.1111/cas.14533

Masatoshi Hara, Tatsuo Fukagawa

Dynamics of kinetochore structure and its regulations during mitotic progression.

Cell. Mol. Life Sci. 77(15):2981-2995.   2020 PMID:32052088 DOI:10.1007/s00018-020-03472-4

Tetsuya Hori, Tatsuo Fukagawa

Artificial generation of centromeres and kinetochores to understand their structure and function.

Exp. Cell Res. 389(2):111898  2020 PMID:32035949 DOI:10.1016/j.yexcr.2020.111898


Reito Watanabe, Masatoshi Hara, Ei-ichi Okumura, Solène Hervé, Daniele Fachinetti, Mariko Ariyoshi, Tatsuo Fukagawa

CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization

J. Cell Biol. 218(12):4042-4062  2019 PMID:31676716 DOI:10.1083/jcb.201907006

Yoshimasa Takizawa, Cheng-Han Ho, Hiroaki Tachiwana, Hideyuki Matsunami, Wataru Kobayashi, Midori Suzuki, Yasuhiro Arimura, Tetsuya Hori, Tatsuo Fukagawa, Melanie D. Ohi, Matthias Wolf, Hitoshi Kurumizaka

Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome

Structure 28(1):44-53.e4  2019 PMID:31711756 DOI:10.1016/j.str.2019.10.016

Hara M, Fukagawa T

Centromere maintenance during DNA replication

Nat. Cell Biol. 21(6):669-671  2019 PMID:31160706 DOI:10.1038/s41556-019-0335-0

Hara M, Fukagawa T

Where is the right path heading from the centromere to spindle microtubules?

Cell Cycle 18(11):1199-1211  2019 PMID:31075048 DOI:10.1080/15384101.2019.1617008

Eykelenboom JK, Gierliński M, Yue Z, Hegarat N, Pollard H, Fukagawa T, Hochegger H, Tanaka TU

Live imaging of marked chromosome regions reveals their dynamic resolution and compaction in mitosis.

J. Cell Biol. 218(5):1531-1552  2019 PMID:30858191 DOI:10.1083/jcb.201807125

Arimura Y, Tachiwana H, Takagi H, Hori T, Kimura H, Fukagawa T, Kurumizaka H

The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism.

Nat. Commun. 10(1):576  2019 PMID:30718488 DOI:10.1038/s41467-019-08314-x


Masatoshi Hara, Mariko Ariyoshi, Ei-ichi Okumura, Tetsuya Hori, Tatsuo Fukagawa

Multiple phosphorylations control recruitment of the KMN-network onto kinetochores

Nat. Cell Biol. 20(12):1378-1388  2018 PMID:30420662 DOI:10.1038/s41556-018-0230-0

Kohei Nishimura, Masataka Komiya, Tetsuya Hori, Takehiko Itoh, Tatsuo Fukagawa

3D genomic architecture reveals that neocentromeres associate with heterochromatin regions

J. Cell Biol. 218(1):134-149  2018 PMID:30396998 DOI:10.1083/jcb.201805003

Fujita H, Tokunaga A, Shimizu S, Whiting AL, Aguilar-Alonso F, Takagi K, Walinda E, Sasaki Y, Shimokawa T, Mizushima T, Ohki I, Ariyoshi M, Tochio H, Bernal F, Shirakawa M, Iwai K

Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization.

Cell Reports 23(4):1192-1204  2018 PMID:29694895 DOI:10.1016/j.celrep.2018.03.112

Hara M, Fukagawa T

Kinetochore assembly and disassembly during mitotic entry and exit.

Curr. Opin. Cell Biol. 52:73-81  2018 PMID:29477052 DOI:10.1016/

Hara M, Lourido S, Petrova B, Lou HJ, Von Stetina JR, Kashevsky H, Turk BE, Orr-Weaver TL

Identification of PNG kinase substrates uncovers interactions with the translational repressor TRAL in the oocyte-to-embryo transition.

eLife 7:e33150  2018 PMID:29480805 DOI:10.7554/eLife.33150

Mills WE, Spence JM, Fukagawa T, Farr CJ

Site-Specific Cleavage by Topoisomerase 2: A Mark of the Core Centromere.

Int. J. Mol. Sci. 19(2):E534  2018 PMID:29439406 DOI:10.3390/ijms19020534


Ishiyama S, Nishiyama A, Saeki Y, Moritsugu K, Morimoto D, Yamaguchi L, Arai N, Matsumura R, Kawakami T, Mishima Y, Hojo H, Shimamura S, Ishikawa F, Tajima S, Tanaka K, Ariyoshi M, Shirakawa M, Ikeguchi M, Kidera A, Suetake I, Arita K, Nakanishi M

Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.

Mol. Cell 68(2):350-360.e7  2017 PMID:29053958 DOI:10.1016/j.molcel.2017.09.037

Hara M, Fukagawa T

Critical Foundation of the Kinetochore: The Constitutive Centromere-Associated Network (CCAN).

Prog Mol Subcell Biol. 56:29-57  2017 PMID:28840232 DOI:10.1007/978-3-319-58592-5_2

Okumura K, Kagawa N, Saito M, Yoshizawa Y, Munakata H, Isogai E, Fukagawa T, Wakabayashi Y

CENP-R acts bilaterally as a tumor suppressor and as an oncogene in the two-stage skin carcinogenesis model.

Cancer Sci. 108(11):2142-2148  2017 PMID:28795467 DOI:10.1111/cas.13348

Nishimura K, Fukagawa T

An efficient method to generate conditional knockout cell lines for essential genes by combination of auxin-inducible degron tag and CRISPR/Cas9.

Chromosome Res. 25(3-4):253-260  2017 PMID:28589221 DOI:10.1007/s10577-017-9559-7

Fukumura T, Makino F, Dietsche T, Kinoshita M, Kato T, Wagner S, Namba K, Imada K, Minamino T

Assembly and stoichiometry of the core structure of the bacterial flagellar type III export gate complex.

PLoS. Biol. 15(8):e2002281  2017 PMID:28771466 DOI:10.1371/journal.pbio.2002281

Hiraoka KD, Morimoto YV, Inoue Y, Fujii T, Miyata T, Makino F, Minamino T, Namba K

Straight and rigid flagellar hook made by insertion of the FlgG specific sequence into FlgE.

Sci Rep 7:46723  2017 PMID:28429800 DOI:10.1038/srep46723

Hori T, Shang WH, Hara M, Ariyoshi M, Arimura Y, Fujita R, Kurumizaka H, Fukagawa T

Association of M18BP1/KNL2 with CENP-A nucleosome is essential for centromere formation in non-mammalian vertebrates

Dev. Cell 42(2):181-189.e3  2017 PMID:28743004 DOI:10.1016/j.devcel.2017.06.019

Tatsuo Fukagawa

Critical histone post-translational modifications for centromere function and propagation

Cell Cycle 16(13):1259-1265  2017 PMID:28840232 DOI:10.1080/15384101.2017.1325044

Masatoshi Hara, Boryana Petrova, Terry L. Orr-Weaver

Control of PNG kinase, a key regulator of mRNA translation, is coupled to meiosis completion at egg activation

eLife 6:e22219  2017 PMID:28555567 DOI:10.7554/eLife.22219

Toyoaki Natsume, Kohei Nishimura, Sheroy Minocherhomji, Rahul Bhowmick, Ian D. Hickson, Masato T. Kanemaki

Acute inactivation of the replicative helicase in human cells triggers MCM8-9-dependent DNA synthesis

Genes Dev. 31(8):816-829  2017 PMID:28487407 DOI:10.1101/gad.297663.117

Vargiu G, Makarov AA, Allan J, Fukagawa T, Booth DG, Earnshaw WC

Stepwise unfolding supports a subunit model for vertebrate kinetochores

Proc. Natl. Acad. Sci. U. S. A. 114(12):3133-3138  2017 PMID:28265097 DOI:10.1073/pnas.1614145114

Hori T, Kagawa N, Toyoda A, Fujiyama A, Misu S, Monma N, Makino F, Ikeo K Fukagawa T

Constitutive centromere-associated network controls centromere drift in vertebrate cells

J. Cell Biol. 216(1):101-113  2017 PMID:27940888 DOI:10.1083/jcb.201605001


Makino F, Shen D, Kajimura N, Kawamoto A, Pissaridou P, Oswin H, Pain M, Murillo I, Namba K, Blocker AJ

The architecture of the cytoplasmic region of type III secretion systems.

Sci Rep 6:33341  2016 PMID:27686865 DOI:10.1038/srep33341

Wei-Hao Shang, Hori T, Westhorpe FG, Godek KM, Toyoda A, Misu S, Monma N, Ikeo K, Carroll CW, Takami Y, Fujiyama A, Kimura H, Straight AF, Fukagawa T

Acetylation of histone H4 Lysine 5 and 12 is required for CENP-A deposition into centromeres

Nat. Commun. 7:13465  2016 PMID:27811920 DOI:10.1038/ncomms13465

Abe T, Kawasumi R, Arakawa H, Hori T, Shirahige K, Losada A, Fukagawa T, Branzei D

Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion.

Oncotarget 7(42):67934-67947  2016 PMID:27636994 DOI:10.18632/oncotarget.11982

Nagpal H, Fukagawa T

Kinetochore assembly and function through the cell cycle.

Chromosoma 125(4):645-59  2016 PMID:27376724 DOI:10.1007/s00412-016-0608-3

Dyomin AG, Koshel EI, Kiselev AM, Saifitdinova AF, Galkina SA, Fukagawa T, Kostareva AA, Gaginskaya ER

Chicken rRNA Gene Cluster Structure.

PLoS One 11(6):e0157464  2016 PMID:27299357 DOI:10.1371/journal.pone.0157464

Nishino T, Fukagawa T

Biochemical and Structural Analysis of Kinetochore Histone-Fold Complexes.

Methods Mol Biol. 1413:135-46  2016 PMID:27193847 DOI:10.1007/978-1-4939-3542-0_9

Tatsuo Fukagawa

Centromeric chromatin and kinetochore assembly in vertebrate cells.

F. Hanaoka, and K. Sugasawa (eds.) DNA replication, recombination, and repair: Molecular Mechanisms and pathology 365-387  2016 DOI:10.1007/978-4-431-55873-6_14

Kusakabe M, Oku H, Matsuda R, Hori T, Muto A, Igarashi K, Fukagawa T, Harata M

Genetic complementation analysis showed distinct contributions of the N-terminal tail of H2A.Z to epigenetic regulations.

Genes Cells 21(2):122-35  2016 PMID:26833946 DOI:10.1111/gtc.12327

Wood L, Booth DG, Vargiu G, Ohta S, deLima Alves F, Samejima K, Fukagawa T, Rappsilber J, Earnshaw WC

Auxin/AID versus conventional knockouts: distinguishing the roles of CENP-T/W in mitotic kinetochore assembly and stability.

Open Biol 6(1):150230  2016 PMID:26791246 DOI:10.1098/rsob.150230

Our ideal candidate (as a graduate student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.


Laboratory of Chromosome Biology, Graduate School of Frontier Biosciences, Osaka University,
1-3 Yamadaoka, Suita, Osaka 565-0871 Japan.


E-mail: tfukagawa[at] (Prof. Tatsuo Fukagawa)

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