Cellular & Molecular Biology Unit

Unit Leader

Takehiko Shibata

  • D.Sci.
  • Takehiko Shibata
  • Brief resume
    1973
    D.Sci., University of Tokyo
    1974
    Research Scientist, Microbiology Laboratory, RIKEN
    1977
    Postdoctoral Associate, Dr. C. M. Radding's Lab, School of Medicine, Yale University, USA
    1985
    Chief Scientist, Microbiology Laboratory, RIKEN
    2001
    Visiting Professor, Graduate School of Nanobioscience, Yokohama City University (-current)
    2005
    Distinguished Senior Scientist, Cellular and Molecular Biology Laboratory, RIKEN
    2010
    Unit Leader, Cellular and Molecular Biology Unit, RIKEN (-current)

Outline

Cellular & Molecular Biology Unit

Homologous DNA (genetic) recombination has two important aspects: it generates genetic diversity through meiotic recombination by, for instance, diversifying antibodies in chickens, and is responsible for vegetative segregation of mitochondrial homoplasmic cells from heteroplasmic cells through recombination-dependent rolling-circle mtDNA-replication. A major goal of our research on recombination is to understand the molecular mechanisms and principles governing homologous recombination in genetic inheritance and evolution. Our basic research on recombination has enabled us to (1) develop the ADLib System for the rapid and immunotolerance-free ex-vivo generation of natural antibodies, and (2) artificially control mitochondrial homoplasmy in cultured eukaryotic cells.

Recent Research Topic

Two sides of homologous DNA recombination: genetic diversification and gene creation in nuclei, and homoplasmy in mitochondria

Independent of ATP requirements and protein structure, homologous pairing proteins (recombinases) induce a common extended structure in bound DNA, which allows the formation of intermolecular double strands between single-stranded and double-stranded DNA molecules
Fig. 1
Independent of ATP requirements and protein structure, homologous pairing proteins (recombinases) induce a common extended structure in bound DNA, which allows the formation of intermolecular double strands between single-stranded and double-stranded DNA molecules

Responding to environmental changes, homologous DNA recombination is induced to diversify genomes for environmental adaptation. We assume a possibility that homologous DNA recombination edits genes using sequence similarity to generate new genes. This assumption and the accumulated achievements of our basic research on homologous recombination led us to invent an “ADLib system,” which generates specific antibodies free of immune-tolerance by artificial induction and suppression of somatic homologous recombination in cultured chicken cells. We also found that homologous DNA recombination plays a role adverse to diversification, that is, the homogenization of multi-copy genomes, “homoplasmy,” in yeast mitochondria.

Selected Publications

  1. N. Arai, et al. Vital roles of the second DNA-binding site of Rad52 in yeast homologous recombination, J. Biol. Chem. 2011, 286, 17607.
  2. J. Inoue, et al. A mechanism for SSB displacement from single-stranded DNA upon SSB-RecO interaction, J. Biol. Chem. 2011, 286, 6720.
  3. F. Ling, T. Mikawa, T. Shibata, Enlightenment of yeast mitochondrial homoplasmy: diversified roles of gene conversion, Genes 2011, 2, 169.
  4. Y. Shingu, T. Mikawa, M. Onuma, T. Hirayama, T. Shibata, A DNA-binding surface of SPO11-1, an Arabidopsis SPO11 orthologue required for normal meiosis, FEBS J. 2010, 277, 2360.
  5. T. Masuda, Y. Ito, T. Terada, T. Shibata, T. Mikawa, A non-canonical DNA structure enables homologous recombination in various genetic systems, J. Biol. Chem. 2009, 284, 30230.
  6. A. Hori, M. Yoshida, T. Shibata, F. Ling, Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication, Nucleic Acids Res. 2009, 37, 749.
  7. F. Ling, M. Yoshida, T. Shibata, Heteroduplex joint formation free of net topological change by Mhr1, a mitochondrial recombinase, J. Biol. Chem. 2009, 284, 9341.
  8. F. Ling, A. Hori, T. Shibata, DNA recombination-initiation plays a role in the extremely biased inheritance of yeast rho-minus mitochondrial DNA that contains the replication origin, ori5, Mol. Cell. Biol. 2007, 27, 1133.
  9. M. Honda, et al. Identification of the RecR toprim domain as the binding site for both RecF and RecO: A role of RecR in RecFOR assembly at dsDNA-ssDNA junctions, J. Biol. Chem. 2006, 281, 18549.
  10. H. Seo, et al. Rapid generation of specific antibodies by enhanced homologous recombination, Nature Biotechnol. 2005, 23, 731.
  11. T. Shibata, et al. Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA/Rad51-family proteins: A possible advantage of DNA over RNA as genomic material, Proc. Natl Acad. Sci. USA 2001, 98, 8425.

Core Members

Principal Investigator add delete
Takehiko Shibata Unit Leader    
Staff Scientist add delete
Tsutomu Mikawa Senior Research Scientist    
Wakana Iwasaki Research Scientist    
Yoshinori Shingu ASI Research Scientist    
Postdoctoral Fellow add delete
Jin Inoue Postdoctoral Researcher    
Akiho Nakamura Visiting Researcher    
Student Trainee add delete
Takeshi Shinohara Junior Research Associate    
Technical Assistant add delete
Administrative Assistant add delete
Visiting Research Staff add delete
Other Staff add delete
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