The strand bias paradox of somatic hypermutation at immunoglobulin loci.
Somatic hypermutation has two phases: phase 1 affects cytosine-guanine (C/G) pairs and is triggered by the deamination of cytosine residues in DNA to uracil; phase 2 affects mostly adenine-thymine (A/T) pairs and is induced by the detection of uracil lesions in DNA. It is not known how, at V(D)J genes in mice, hypermutations accumulate at A/T pairs with strand bias without perturbing the strand unbiased accumulation of hypermutations at C/G pairs. Additionally, it is not known why, in contrast, at switch regions in mice, both C/G-targeted and A/T-targeted hypermutations accumulate in a strand unbiased manner. To explain the strand bias paradox, we propose that phase 1 and phase 2 hypermutations are generated at different stages of the cell cycle.
Franklin
Andrew
A
The Immune Disease Institute, The Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. franklin@idi.harvard.edu
Blanden
Robert V
RV
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics* / Q000276:immunology; D020029:Base Pairing; D002453:Cell Cycle / Q000235:genetics; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D016296:Mutagenesis; D027041:Somatic Hypermutation, Immunoglobulin
D007136:Immunoglobulins