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Cellular & Molecular Biology Unit
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Unit Leader
Takehiko SHIBATA (D.Sci.)
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Research Areas

The major goal of our research is to understand the molecular mechanisms and principles governing homologous DNA (or genetic) recombination in genetic inheritance and evolution. Homologous recombination is the rearrangements of segments between a pair of homologous DNAs, and plays a role in error-free DNA double-stranded break repair for the genome stability, by using homologous DNA as a template for the repair. On the other hand, it is assumed, and has partly been proven by our "ADLib system", that in response to environmental changes, using preceding DNA sequences, homologous recombination creates new genes for adapting to pathogens and new environments, such as antibody production. A key reaction in homologous recombination is "homologous pairing", in which a single-stranded DNA tail derived from an end of a double-stranded break, is base-paired with a complementary sequence in a template double-stranded DNA. I discovered RecA-catalyzed homologous pairing, which requires ATP (Shibata et al., 1979 PNAS). We found a new class of homologous pairing proteins, which do not require ATP (Kagawa et al., 2001 JBC: Ling & Shibata, 2002 EMBO J). Using NMR, we found that a unique extended DNA structure was induced in the common homologous pairing intermediates by both the RecA-family proteins (RecA, Rad51) and the new class of homologous pairing proteins from various origins (Masuda et al., 2009 JBC). These findings indicate that homologous pairing does not depend on a particular group of proteins, but rather is an intrinsic molecular function of DNA (Shibata et al., 2001 PNAS for review). We found the novel roles of a homologous pairing protein in DNA-replication, partitioning and homoplasmy (a type of gene homogenization) in yeast mitochondrial DNA inheritance, in which ROS (reactive oxygen species) act as a regulatory mediator (Hori et al., NAR 2009; see Ling & Shibata 2011 for review). The development of new genome-wide technologies is within our scope. We invented the ADLib System, for the rapid and immunotolerance-free ex-vivo production of natural antibodies (Seo et al., 2005 Nature Biotech).

Research Subject

  1. Biochemistry and molecular and structural biology on the initiation of gene conversion
  2. Molecular regulation on the initiation of plant homologous recombination and its applications
  3. The functions of genetic recombination in mitochondrial genetic inheritance

Related links

  1. RIKEN Advanced Science Institute Website_Laboratories PageNew Window
  2. Laboratory of Molecular & Cellular Physiology PageNew Window

RIKEN RESEARCH

January 30, 2009
An 'opening' role
Non-coding RNAs play a role in regulating the expression of genes in yeast New Window
May 30, 2008
Keeping everything in order
Investigators may have uncovered a molecular 'switch' that ensures that processes relating to cell division occur in the proper sequence New Window

List of Selected Publications

  1. Arai, N., Kagawa, W., Saito, K., Shingu, Y., Mikawa, T., Kurumizaka, H. and Shibata, T.:
    "Vital roles of the second DNA-binding site of Rad52 in yeast homologous recombination"
    J. Biol. Chem., 286, 17607-17617 (2011).
  2. Inoue, J., Nagae, T., Mishima, M., Ito, Y., Shibata, T. and Mikawa, T.:
    "A mechanism for SSB displacement from single-stranded DNA upon SSB-RecO interaction"
    J. Biol. Chem., 286, 6720-6732 (2011).
  3. Ling, F., Mikawa, T. and Shibata, T.:
    "Enlightenment of yeast mitochondrial homoplasmy: diversified roles of gene conversion"
    Genes, 2, 169-190 (2011).
  4. Shingu, Y., Mikawa, T., Onuma, M., Hirayama, T. and Shibata, T.:
    "A DNA-binding surface of SPO11-1, an Arabidopsis SPO11 orthologue required for normal meiosis"
    FEBS J., 277, 2360-2374 (2010).
  5. Masuda, T., Ito, Y., Terada, T., Shibata, T. and Mikawa, T.:
    "A non-canonical DNA structure enables homologous recombination in various genetic systems"
    J. Biol. Chem., 284, 30230-30239 (2009).
  6. Seo, H., Masuoka, M., Murofushi, H., Takeda, S., Shibata, T. and Ohta, K.:
    "Rapid generation of specific antibodies by enhanced homologous recombination"
    Nature Biotechnol., 23, 731-735 (2005).
  7. Kagawa, W., Kurumizaka, H., Ikawa, S., Yokoyama, S. and Shibata, T.:
    "Homologous pairing promoted by the human Rad52 protein"
    J. Biol. Chem., 276, 35201-35208 (2001).
  8. Shibata, T., Nishinaka, T., Mikawa, T., Aihara, H., Kurumizaka, H., Yokoyama, S. and Ito, Y.:
    "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, 98, 8425-8432 (2001).
  9. Nishinaka, T., Ito, Y., Yokoyama, S. and Shibata, T.:
    "An extended DNA structure through deoxyribose-base stacking induced by RecA protein"
    Proc. Natl. Acad. Sci. USA, 94, 6623-6628 (1997).
  10. Shibata, T., DasGupta, C., Cunningham, R. P. and Radding, C. M.:
    "Purified Escherichia coli recA protein catalyzes homologous pairing of superhelical DNA and single-stranded fragments"
    Proc. Natl. Acad. Sci. USA, 76, 1638-1642 (1979).

Members

Principal Investigator

Takehiko SHIBATA
Unit Leader

Staff Scientist

Tsutomu MIKAWA
Senior Research Scientist
Wakana IWASAKI
Research Scientist
Yoshinori SHINGU
ASI Research Scientist

Student Trainee

Takeshi SHINOHARA
Junior Research Associate
Naoto KONOMURA
Junior Research Associate

Technical Assistant

Yukari IIKURA
Technical Staff II
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