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2005 Fiscal Year Final Research Report Summary

Molecular mechanism of class switch recombination and somatic hypermutation.

Research Project

Project/Area Number 16590401
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

SHINKURA Reiko  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 寄付講座講師 (50362471)

Project Period (FY) 2004 – 2005
Keywordsantibody / AID / class switch recombination / somatic hypermutation / humoral immune response
Research Abstract

Activation-induced cytidine deaminase (AID) is the essential molecule for class switch recombination (CSR) and somatic hypermutation (SHM). CSR is a region-specific recombination that takes place between switch (S) regions. SHM introduces point mutations in the variable (V) region. We are asking two following questions.
1. How does AID regulate differentially CSR and SHM?
We have shown that mutants with alterations in the C-terminal region of AID retain normal SHM activity but almost completely lose CSR activity. In addition, we found that mutations in the N-terminal region of AID resulted in specific loss of SHM activity but retained CSR activity. Those mutations do not locate in the cytidine deaminase motif of AID, indicating that CSR and SHM activities of AID are regulated differentially through the interaction of CSR- or SHM-specific cofactors with C-terminus or N-terminus of AID, respectively. For in vivo study, we will generate the AID knock-in mice those express the N- or C-terminal AID mutants instead of wild-type AID.
2. What is the target of AID?
AID is important for the initiation of DNA cleavage in S region. However, how AID initiates DNA cleavage is still controversial. All other researchers except for us believe that AID deaminates cytocine on DNA, resulting in DNA double strand breakage in collaboration with UNG. However, we think that AID is an RNA editing enzyme, which edits mRNA to encode the putative endonuclease, resulting in DNA cleavage. We synthesized and purified AID by in vitro transcription/translation system. In vitro synthesized AID showed the cytidine deaminase activity on single-stranded DNA, whereas deaminase-deficient AID mutant did not. It indicates that in vitro synthesized AID has cytidine deaminase activity on DNA. Next, using this AID protein, we are going to show that AID edits RNA, too.

  • Research Products

    (6 results)

All 2005 2004

All Journal Article (6 results)

  • [Journal Article] AID to overcome the limitations of genomic information.2005

    • Author(s)
      Honjo, T. et al.
    • Journal Title

      Nature Immunology 6(7)

      Pages: 655-661

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] AID to overcome the limitations of genomic information.2005

    • Author(s)
      Honjo, T. et al.
    • Journal Title

      Nature Immunology 6

      Pages: 655-661

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Separate domains of AID are required for somatic hypermutation and class-switch recombination.2004

    • Author(s)
      Shinkura, R. et al.
    • Journal Title

      Nature Immunology 5

      Pages: 707-712

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch.2004

    • Author(s)
      Begum, NA. et al.
    • Journal Title

      Science 305

      Pages: 1160-1163

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] De novo protein synthesis is required for activation-induced cytidine deaminase- dependent DNA cleavage in immunoglobulin class switch recombination.2004

    • Author(s)
      Begum, NA. et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 101

      Pages: 13003-13007

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] De novo protein synthesis is required for activation-induced cytidine deaminase-dependent DNA cleavage in immunoglobulin class switch recombination.2004

    • Author(s)
      Begum, NA. et al.
    • Journal Title

      Proc.Natl Acad.Sci.USA 101

      Pages: 13003-13007

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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