A/T-targeted somatic hypermutation: critique of the mainstream model

Trends in Biochemical Sciences
Andrew Franklin, Robert V Blanden

Abstract

The "affinity maturation" of the humoral immune response is driven by antigen-activated somatic hypermutation (SHM) of the genes that encode antibody variable regions and the subsequent antigenic selection of mutant clones. The molecular mechanism of SHM is yet to be completely elucidated. SHM affects cytosine-guanine (C/G) and adenine-thymine (A/T) pairs with approximately equal frequency in vivo. The proposition that error-prone DNA-dependent DNA synthesis explains A/T-targeted hypermutagenesis seems to have mainstream support within the hypermutation research community at present. A major feature of SHM in vivo is that C/G hypermutation is strand unbiased, whereas A/T hypermutation is strand biased. We show that the "DNA-based polymerase error" model of A/T-targeted hypermutagenesis does not explain this important aspect of SHM.

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Citations

May 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mary Anne T RubioJuan D Alfonzo
Jun 20, 2007·Annual Review of Genetics·Grace Teng, F Nina Papavasiliou
Nov 8, 2011·Molecular Immunology·Barbara E WrightMichael F Minnick
Feb 26, 2011·Developmental and Comparative Immunology·Vasco M Barreto, Brad G Magor
Mar 11, 2008·Trends in Immunology·Andrew Franklin, Robert V Blanden
Sep 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Benjamin RocheFrançois Rougeon

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