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Somatic hypermutation

Experiments in fibroblasts have identified an enzyme that induces hypermutation resembling the hypermutator of immunoglobulin genes in lymphocytes.

Jonathan Weitzman(jonathanweitzman@hotmail.com)

Somatic hypermutation, gene conversion and class-switch recombination are genetic rearrangements that generate the molecular diversity of immunoglobulin genes underlying the human immune system. In the 14 June Science, Kiyotsugu Yoshikawa and colleagues report that a single enzyme, activation-induced cytidine deaminase (AID), is sufficient to generate somatic hypermutation in fibroblasts cells (Science 2002, 296:2033-2036).

To examine hypermutation, Yoshikawa et al. created an NIH3T3 fibroblast cell line expressing a tetracycline-regulated mutant green fluorescent protein (GFP) gene containing a premature stop codon. They were able to select GFP-positive cells (around 1-1.8% of cells) following introduction of functional AID, but not an inactive AID isoform. The mutation rate increased with the level of transcriptional induction of GFP.

They found large numbers of mutations in the GFP gene when the target gene was transcribed (4.5 x 10-4 mutations per base pair per generation). The type of AID-induced mutations resembled those...

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