Article abstract
Nature Structural & Molecular Biology 16, 769 - 776 (2009)
Published online: 21 June 2009 | doi:10.1038/nsmb.1623
AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity
Meng Wang1, Zizhen Yang1, Cristina Rada1 & Michael S Neuberger1
Abstract
DNA deaminases underpin pathways in antibody diversification (AID) and anti-viral immunity (APOBEC3s). Here we show how a high-throughput bacterial papillation assay can be used to screen for AID mutants with increased catalytic activity. The upmutations focus on a small number of residues, some highlighting regions implicated in AID's substrate interaction. Many of the upmutations bring the sequence of AID closer to that of APOBEC3s. AID upmutants can yield increased antibody diversification, raising the possibility that modification of AID's specific activity might be used to regulate antibody diversification in vivo. However, upmutation of AID also led to an increased frequency of chromosomal translocations, suggesting that AID's specific activity may have been limited by the risk of genomic instability.
- Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
Correspondence to: Michael S Neuberger1 e-mail: msn@mrc-lmb.cam.ac.uk
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