Laboratories / Div. of Research Resources & Support

Molecular Radiology /
Sec. of Radiation Biology

Professor: Kiyoshi Miyagawa
Lecturer: Takahiko Suzuki
Lecturer: Noriko Hosoya
Assistant Prof.: Atsushi Enomoto

1. Research
On the basis of radiation biology, particularly the mechanisms of DNA double strand break repair, which is the most serious effect of radiation, we are investigating molecular pathology of diseases induced by genome instability, novel cancer therapies, and a novel methodology for gene manipulation. The DNA double strand break repair pathways mainly consist of non-homologous end-joining (NHEJ) and homologous recombination (HR). Because NHEJ was assumed to play a critical role in radiation sensitivity, the NHEJ pathway has been well characterized so far. However, recent studies have shown that HR also plays a role in radiation sensitivity at some stages of the cell cycle in mammals. Furthermore, HR is now regarded as an important field in oncology, because HR has been shown to play a causal role in breast cancer. We are focusing on the following projects.

  1. The mechanisms of homologous recombination repair in human cells.
  2. The molecular mechanisms of chromosome instability.
  3. Radiation biology-based medical oncology.
2. Publications
  1. Hosoya N, Okajima M, Kinomura A, Fujii Y, Hiyama T, Sun J, Tashiro S, Miyagawa K: Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA2. EMBO Rep 13: 44-51, (2012)
  2. Katsura M, Tsuruga T, Date O, Yoshihara T, Ishida M, Tomoda Y, Okajima M, Takaku M, Kurumizaka H, Kinomura A, Mishima HK, Miyagawa K: The ATR-Chk1　pathway plays a role in the generation of centrosome aberrations induced by　Rad51C dysfunction. Nucleic Acids Res 37: 3959-3968, (2009)
  3. Enomoto A, Kido N, Ito M, Morita A, Matsumoto Y, Takamatsu N, Hosoi Y, Miyagawa K: Negative regulation of MEKK1/2 signaling by Serine-Threonine Kinase 38 (STK38). Oncogene 27: 1930-1938, (2008)
  4. Hiyama T, Katsura M, Yoshihara T, Ishida M, Kinomura A, Tonda T, Asahara T, Miyagawa K: Haploinsufficiency of the Mus81-Eme1 endonuclease activates the intra-S-phase and G2/M checkpoints and promotes rereplication in human cells. Nucleic Acids Res 34: 880-892, (2006)
  5. Nobukuni Y, Kohno K, Miyagawa K: Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphthamide on elongation factor 2. J Biol Chem 280: 10572-10577, (2005)
  6. Kinebuchi T, Kagawa W, Enomoto R, Tanaka K, Miyagawa K, Shibata T, Kurumizaka H, Yokoyama S: Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1. Mol Cell 14: 363-374, (2004)
  7. Yoshihara T, Ishida M, Kinomura A, Katsura M, Tsuruga T, Tashiro S, Asahara T, Miyagawa K: XRCC3 deficiency results in a defect in recombination and increased endoreduplication in human cells. EMBO J 23: 670-680, (2004)