Premium
Understanding the spread of mutations during somatic hypermutation
Author(s) -
Unniraman Shyam,
Schatz David G.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.849.3
Subject(s) - somatic hypermutation , cytidine deaminase , deamination , genetics , biology , activation induced (cytidine) deaminase , mutation , somatic cell , dna , cytosine , mutagenesis , gene , biochemistry , enzyme , b cell , antibody
Somatic hypermutation of antibody genes is initiated by the deamination of cytosines to uracils in DNA by activation induced deaminase (AID). However, the process that leads from the initiating deamination event at cytosines to mutations at other residues remains poorly understood. Using a novel transgenic mouse model system, here, we demonstrate that a single cytosine on the top (non‐template) strand is sufficient to recruit AID and lead to mutations of both upstream and downstream A/T residues up to 29 bp away. In contrast, although cytosines on the bottom strand are targeted by AID, this does not lead to substantial mutation of neighboring residues. This strand asymmetry is eliminated in mice that are deficient in mismatch repair, indicating that error‐prone mismatch repair preferentially targets top strand uracils during somatic hypermutation. We are currently testing the influence of other repair factors on the orientation and extent of the spread. Research funded by Howard Hughes Medical Institute .