IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v419y2002i6902d10.1038_nature00981.html
   My bibliography  Save this article

Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase

Author

Listed:
  • Javier Di Noia

    (Medical Research Council Laboratory of Molecular Biology)

  • Michael S. Neuberger

    (Medical Research Council Laboratory of Molecular Biology)

Abstract

A functional immune system depends on the production of a wide range of immunoglobulin molecules. Immunoglobulin variable region (IgV) genes are diversified after gene rearrangement by hypermutation. In the DNA deamination model, we have proposed that deamination of dC residues to dU by activation-induced deaminase (AID) triggers this diversification. In hypermutating chicken DT40 B cells, most IgV mutations are dC → dG/dA or dG → dC/dT transversions, which are proposed to result from replication over sites of base loss produced by the excision activity of uracil-DNA glycosylase. Blocking the activity of uracil-DNA glycosylase should instead lead to replication over the dU lesion, resulting in dC → dT (and dG → dA) transitions. Here we show that expression in DT40 cells of a bacteriophage-encoded protein that inhibits uracil-DNA glycosylase shifts the pattern of IgV gene mutations from transversion dominance to transition dominance. This is good evidence that antibody diversification involves dC → dU deamination within the immunoglobulin locus itself.

Suggested Citation

  • Javier Di Noia & Michael S. Neuberger, 2002. "Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase," Nature, Nature, vol. 419(6902), pages 43-48, September.
    • Handle: RePEc:nat:nature:v:419:y:2002:i:6902:d:10.1038_nature00981
    DOI: 10.1038/nature00981
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature00981
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature00981?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Philip Barbulescu & Chetan K. Chana & Matthew K. Wong & Ines Ben Makhlouf & Jeffrey P. Bruce & Yuqing Feng & Alexander F. A. Keszei & Cassandra Wong & Rukshana Mohamad-Ramshan & Laura C. McGary & Moha, 2024. "FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:419:y:2002:i:6902:d:10.1038_nature00981. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.