Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

The mechanism of somatic hypermutation at A·T pairs remains an open question

Nature Reviews Immunology volume 5, page 180 (2005)Cite this article

Access through your institution
Buy or subscribe

Reply

There are many indications that the mutations at A·T (deoxyadenosine·deoxythymidine) pairs during somatic hypermutation (SHM) are introduced by mutagenic patch repair of activation-induced deaminase (AID)-generated U·G (deoxyuridine· deoxyguanosine) lesions. Franklin and Blanden rightly state that a popular model is that these mutations are caused by DNA-polymerase-catalysed incorporation of improperly paired bases during the patch-repair process (that is, polymerase error), whereas we have recently postulated that DNA-polymerase-catalysed incorporation of U residues, instead of T residues, opposite A residues might provide an alternative mechanism (that is, dUTP (deoxyuridine triphosphate) incorporation)1.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Neuberger, M. S . et al. Somatic hypermutation at A·T pairs: polymerase error verus dUTP incorporation. Nature Rev. Immunol. 5, 171–178 (2005).

    Article  CAS  Google Scholar 

  2. Zeng, X . et al. DNA polymerase η is an A–T mutator in somatic hypermutation of immunoglobulin variable genes. Nature Immunol. 2, 537–541 (2001).

    Article  CAS  Google Scholar 

  3. Delbos, F., De Smet, A, Faili, A, Aoufouchi, S, Weill, J. C. & Reynaud, C. A. Contribution of DNA polymerase η to immunoglobulin gene hypermutation in the mouse. J. Exp. Med. 201, 1191–1196 (2005).

    Article  CAS  Google Scholar 

  4. Martomo, S. A . et al. Different mutation signatures in DNA polymerase η- and MSH6-deficient mice suggest separate roles in antibody diversification. Proc. Natl Acad. Sci. USA 102, 8656–8661 (2005).

    Article  CAS  Google Scholar 

  5. Matsuda, T, Bebenek, K, Masutani C., Hanaoka, F. & Kunkel, T. A. Low fidelity DNA synthesis by human DNA polymerase-η. Low fidelity DNA synthesis by human DNA polymerase-η. Nature 404, 1011–1013 (2000).

    Article  CAS  Google Scholar 

  6. Matsuda, T . et al. Error rate and specificity of human and murine DNA polymerase-η. J. Mol. Biol. 312, 335–346 (2001).

    Article  CAS  Google Scholar 

  7. Rogozin, I. B, Pavlov, Y. I, Bebenek, K, Matsuda, T. & Kunkel, T. A. Somatic mutation hotspots correlate with DNA polymerase η error spectrum. Nature Immunol. 2, 530–536 (2001).

    Article  CAS  Google Scholar 

  8. Rada, C . et al. Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Curr. Biol. 12, 1748–1755 (2002).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Michael S. Neuberger, Javier M. Di Noia, Rupert C. L. Beale, Gareth T. Williams, Zizhen Yang & Cristina Rada

Authors
  1. Michael S. Neuberger
    View author publications

    Search author on:PubMed Google Scholar

  2. Javier M. Di Noia
    View author publications

    Search author on:PubMed Google Scholar

  3. Rupert C. L. Beale
    View author publications

    Search author on:PubMed Google Scholar

  4. Gareth T. Williams
    View author publications

    Search author on:PubMed Google Scholar

  5. Zizhen Yang
    View author publications

    Search author on:PubMed Google Scholar

  6. Cristina Rada
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neuberger, M., Di Noia, J., Beale, R. et al. The mechanism of somatic hypermutation at A·T pairs remains an open question. Nat Rev Immunol 5, 180 (2005). https://doi.org/10.1038/nri1553-c2

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nri1553-c2

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing