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

Javier Di Noia and Michael S. Neuberger ()
Additional contact information
Javier Di Noia: Medical Research Council Laboratory of Molecular Biology
Michael S. Neuberger: Medical Research Council Laboratory of Molecular Biology

Nature, 2002, vol. 419, issue 6902, 43-48

Abstract: 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.

Date: 2002
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature00981 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:419:y:2002:i:6902:d:10.1038_nature00981

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature00981

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().