Laboratory of Cellular Regulation



Professor:                 Hirofumi Tanaka, PhD                           E-mail: tanaka(at)

Assistant Professor: Yoshitami Hashimoto, PhD                    E-mail: hashimo(at)

Graduate Students:  Yuto Uemura (M2), Koki Miyazawa (M2), Yohei Kobayashi (M1),

                                Kosuke Mizutani (M1)

Undergraduates:      Yuki Ino, Hiroka Shimizu, Chiaki Kodama, Yuri Tanaka, Emi Fijita,

                                 Maho Furukawa, Kenta Yamada


Laboratory of Cellular Regulation

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences

1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Research Project

We are focusing on the studies of regulatory mechanisms of cell cycle progression, especially of DNA replication and mitosis.

  1. 1)Biochemical analysis of the dynamics of DNA replication forks and replisome in the presence of DNA damage. 

A collision of a replication fork with DNA damage induces fork stalling or occasionally fork collapse and severely impairs replication progression, which underlay the basic concept of cancer treatment by DNA damaging agent. But the dynamics of a fork-associated replisome complex during fork stalling/collapse is poorly understood. Those stalled or collapsed replication forks are assumed to be re-activated via several pathways, which is also not well understood. We are investigating those issues mainly by using Xenopus egg extract, which can reproduce eukaryotic genome replication and DNA damage response in vitro.

  1. 2)Molecular and biochemical analysis of the function of a novel ubiquitin ligase on chromosome stability, separation and cytokinesis.

We previously identified a novel ubiquitin ligase named H10BH, which interacts with UbcH10, a mitosis-specific E2 in the ubiqutin/proteasome system, and demonstrated that H10BH interacts with cyclin B amd facilitates its ubiquitilation in vitro (Kobirumaki et al, J. Biochem., 2005), but the exact role of H10BH in vivo is not understood. In the two hybrid screening we also found H10BH interacts with many other cell cycle related proteins, suggesting multiple roles of H10BH in the cell cycle progression. We are trying to clarify them using mammalian cell culture and Xenopus egg extract.

Recent Publications (past 5 years)

  1. 1.Topoisomerase I poisoning results in PARP-mediated replication fork reversal. Ray Chaudhuri A, Hashimoto Y, Herrador R, Neelsen KJ, Fachinetti D, Bermejo R, Cocito A, Costanzo V, Lopes M. Nat Struct Mol Biol. 19, 417-23 (2012).

  2. 2.RAD51- and MRE11-depedent reassembly of uncoupled CMG helicase complex at collapsed replication forks. Hashimoto Y, Puddu F, Costanzo V. Nat Struct Mol Biol. 19, 17-24 (2012)

  3. 3.Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis. Hashimoto Y, Ray Chaudhuri A, Lopes M, Costanzo V. Nat Struct Mol Biol. 17, 1305-11 (2010)

  4. 4.Ban, R., Matsuzaki, H., Akashi, T., Sakashita, G., Taniguchi, H., Park, S.Y., Tanaka, H., Furukawa, K., Urano T. Mitotic regulation of the stability of microtubule plus-end tracking protein EB3 by ubiquitin ligase SIAH-1 and Aurora mitotic kinases. J. Biol. Chem., 284 (41) :28367-28381, 2009

  5. 5.Mizoguchi, T., Muto, A., Udagawa, N., Arai, A., Yamashita, T., Hosoya, A.,Ninomiya, T., Nakamura, H., Yamamoto, Y., Kinugawa, S., Nakamura, M., Nakamichi, Y., Kobayashi, Y., Nagasawa, S., Oda, K., Tanaka, H., Tagaya, N., Penninger, J.M., Ito, M., and Takahashi, N. Identification of cell cycle-arrested quiescent osteoclast precursors in vivoJ. Cell Biol., 184 (4): 541-554, 2009