AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification

Svend K. Petersen-Mahrt, Reuben S. Harris, Michael S. Neuberger

Research output: Contribution to journalArticlepeer-review

706 Scopus citations

Abstract

After gene rearrangement, immunoglobulin variable genes are diversified by somatic hypermutation or gene conversion, whereas the constant region is altered by class-switch recombination. All three processes depend on activation-induced cytidine deaminase (AID), a B-cell-specific protein that has been proposed (because of sequence homologyI) to function by RNA editing. But indications that the three gene diversification processes might be initiated by a common type of DNA lesion, together with the proposal that there is a first phase of hypermutation that targets dC/dG, suggested to us that AID may function directly at dC/dG pairs. Here we show that expression of AID in Escherichia coli gives a mutator phenotype that yields nucleotide transitions at dC/dG in a context-dependent manner. Mutation triggered by AID is enhanced by a deficiency of uracil-DNA glycosylase, which indicates that AID functions by deaminating dC residues in DNA. We propose that diversification of functional immunoglobulin genes is triggered by AID-mediated deamination of dC residues in the immunoglobulin locus with the outcome - that is, hypermutation phases 1 and 2, gene conversion or switch recombination - dependent on the way in which the initiating dU/dG lesion is resolved.

Original languageEnglish (US)
Pages (from-to)99-103
Number of pages5
JournalNature
Volume418
Issue number6893
DOIs
StatePublished - Jul 4 2002

Fingerprint Dive into the research topics of 'AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification'. Together they form a unique fingerprint.

Cite this