Department of Molecular Biology

Notice: The 12th 3R&3C International Symposium (Nov. 18-22, 2024)

Faculty members

Tsutomu Katayama, Ph.D. , Professor

Shogo Ozaki, Ph.D., Associate Professor

Kazutoshi Kasho, Ph. D., Assistant Professor

Related, brief history
(Hironori Kawakami, Ph.D., a previous Reseach Associate is currently an Uehara Foundation (later, a JSPS) post-doctoral fellow in Dr. Bruce Stillman Laboratory of CSHL.) ---> Assistant Professor from March 2012--->Associate Professor of Sanyo Onoda-City University

(Msayuki Su'etsugu, Ph.D., a previous Reseach Associate is currently a JSPS post-doctoral fellow in Dr. Jeff Errington Laboratory.) ---> Assistant Professor from October 2011 ----> From April 2013, Associate Professor of Rikkyo University

(Kazuyuki Fujimitsu, Ph.D., a previous Reseach Associate is currently a post-doctoral fellow in Dr. Yamano Laboratory in UCL Cancer Institute, University College London .)

(Shogo Ozaki, Ph.D., a previous Reseach Associate is currently an Uehara Foundation post-doctoral fellow in Dr. Urs Jenal Laboratory in Biozentrum of University of Basel.) ----> Associate Professor

(Kenji Keyamura, Ph.D., a previous Reseach Associate is currently an Assistant Professor of Gakushuin University in Tokyo.)


In the cell cycle progression, chromosomal DNA is replicated only once at a specific time by the carefully controlled molecular switch for replicational initiation. If this regulation is interfered with, various cell defects occur, such as abnormal chromosomes, inhibition of cell division, and growth of abnormal cells. Thus, a study on this regulatory mechanism is of significance as a basis for the developments of antibiotics and anticancer drugs. We have shown that a protein (DnaA) initiating E. coli chromosomal replication is inactivated by timely and direct interaction with a subunit (beta subunit) of chromosomal replicase (DNA polymerase III holoenzyme). This interaction depends on loading the subunit onto DNA. This conformational change occurs for the nucleotide-polymerizing action of the replicase after the initiation reaction by DnaA. Thus, during the cell cycle, the initiation protein is most likely inactivated just after initiation of chromosomal replication in this manner. We have termed this regulatory system RIDA (Regulatory inactivation of DnaA). Reactivation of DnaA will occur before the next round of the replication cycle. We are investigating the molecular mechanisms in this DnaA-activity cycle including timely inactivation and activation.

Important references

Benjamin Lewin (2004) "GENES VIII, International Edition"
 CHAPTER 14  DNA Replication  (RIDA is described on p410-411)


Skarstad, K. and Katayama, T. (2013)
Regulating DNA Replication in Bacteria
In "DNA Replication", Edited by Bell, S.D., Me'chali, M, and DePamphilis, M.L., Cold Spring Harbor Laboratory Press

Katayama, T., Ozaki, S., Keyamura, K. and Fujimitsu, K. (2010)
Regulation of the replication cycle: Conserved and diverse regulatory systems for DnaA and oriC
Nature Rev. Microbiol.

Ozaki, S., and Katayama, T. (2009)
DnaA structure, function, and dynamics in the initiation at the chromosomal origin
Plasmid 62: 71- 82

Katayama, T.(2001)
Feedback controls restrain the initiation of Escherichia coli chromosomal replication.

Selected original papers

Ozaki, S., Matsuda, Y., Keyamura, K., Kawakami, H., Noguchi, Y., Kasho, K., Nagata, K., Masuda, T., Sakiyama, Y., and Katayama, T. (2013)
A replicase clamp-binding dynamin-like protein promotes colocalization of the nascent DNA strands and equipartitioning of chromosomes in E. coli
Cell Reports(

Kasho K., and Katayama,T. (2013)
DnaA-binding locus datA promotes DnaA-ATP hydrolysis to enable cell cycle-coordinated replication initiation
Proc. Natl. Acad. Sci. USA 110, 946-941

Ozaki, S., and Katayama, T. (2012)
Highly organized DnaA-oriC complexes recruit the single-stranded DNA for replication initiation
Nucleic Acids Res. 40(4), 1648-1665

Fujimitsu, K., Senriuchi, T., and Katayama, T. (2009)
Specific genomic sequences of E. coli promote replicational initiation by directly reactivating ADP-DnaA
Genes Dev. 23(10): 1221-1233 (Perspectives, 23(10):1145-50) 

Ozaki, S., Kawakami,H., Nakamura, K., Fujikawa, N., Kagawa, W., Park, S.-Y., Yokoyama, S., Kurumizaka, H., and Katayama, T. (2008)
A common mechanism for the ATP-DnaA-dependent formation of open complexes at the replication origin
J. Biol. Chem. 283(13), 8351-8362

Keyamura, K., Fujikawa, N.(Equal contributors), Ishida, T., Ozaki, S., Su'etsugu, M., Fujimitsu, K., Kagawa, W., Yokoyama, S., Kurumizaka, H.* and Katayama, T.* (*Co-corresponding authos) (2007)
The interaction of DiaA and DnaA regulates the replication cycle in E. coli by directly promoting ATP-DnaA-specific initiation complexes
Genes Dev. 21, 2083-2099

Abe, Y., Jo, T., Matsuda, Y., Matsunaga, C., Katayama, T.*, and Ueda, T.* (*Co-corresponding authors) (2007)
Structure and function of DnaA N-terminal domains: Specific sites and mechanisms in inter-DnaA interaction and in DnaB helicase loading on oriC
J. Biol. Chem. 282(24),17816-17827 JBC Paper of the Week

Ozaki, S., Fujimitsu, K., Kurumizaka, H., and Katayama, T. (2006)
The DnaA homolog of the hyperthermophilic eubacterium Thermotoga maritima forms an open complex with a minimal 149-bp origin region in an ATP-dependent manner
Genes Cells 11, 425-438

Kawakami, H., Ozaki, S. (Equal contributors), Suzuki, S., Nakamura, K., Senriuchi, T., Su'etsugu, M., Fujimitsu, K., and Katayama, T. (2006)
The exceptionally tight affinity of DnaA for ATP/ADP requires a unique aspartic acid residue in the AAA+ sensor 1 motif
Mol. Microbiol. 62(5), 1310-1324

Kawakami, H., Keyamura, K., and Katayama, T. (2005)
Formation of an ATP-DnaA-specific initiation complex requires DnaA arginine-285, a conserved motif in the AAA+ protein family
J. Biol. Chem. 280(29), 27420-27430

Su'etsugu, M, Shimuta, T., Ishida, T., Kawakami, H. and Katayama, T. (2005)
Protein associations in DnaA-ATP hydrolysis mediated by the replicase clamp-Hda complex
J. Biol. Chem. 280(8), 6528-6536

Fujikawa, N., Kurumizaka, H., Nureki, O., Terada, T., Shirouzu, M., Katayama, T., and Yokoyama, S. (2003)
Structural basis of replication origin recognition by the DnaA protein
Nucleic Acid Res. 31(8), 2077-2086

Nishida, S., Fujimitsu, K., Sekimizu, K., Ohmura,T., Ueda, T., and Katayama, T.(2002)
A nucleotide switch in E.coli DnaA protein initiates chromosomal replication: Evidence from a mutant DnaA protein defective in regulatory ATP hydrolysis in vitro and in vivo.
J.Biol.Chem. 277(17),14986-14995

Kato,J. and Katayama, T.(2001)
Hda,a novel DnaA-related protein,regulates the replication cycle in Escherichia coli.
EMBO J. 20(15),4253-4262

Kurokawa, K., Nishida, S., Emoto, A., Sekimizu, K.,and Katayama, T.(1999)
Replication cycle-coordinated change of the adenine nucleotide-bound forms of DnaA protein in Escherichia coli.
EMBO J. 18(23),6642-6652

Katayama, T., Kubota, T., Kurokawa, K., Crooke, E.,and Sekimizu, K.(1998)
The initiation function of DnaAprotein is negatively regulated by the sliding clamp of the sliding clamp of the E.coli chromosomal replicase.
Cell 94(1),61-71