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Publication : DNA double-strand breaks in immunoglobulin genes undergoing somatic hypermutation.

First Author  Bross L Year  2000
Journal  Immunity Volume  13
Issue  5 Pages  589-97
PubMed ID  11114372 Mgi Jnum  J:66031
Mgi Id  MGI:1927742 Doi  10.1016/s1074-7613(00)00059-5
Citation  Bross L, et al. (2000) DNA double-strand breaks in immunoglobulin genes undergoing somatic hypermutation. Immunity 13(5):589-97
abstractText  How rearranged immunoglobulin (Ig) genes are further diversified by somatic hypermutation is unknown. Using VDJ passenger Ig heavy chain (IgH) knockin mouse strains, we now demonstrate a high frequency of DNA double-strand breaks (DSBs) in the targeted VDJ passenger gene of germinal center (GC) B cells. These DSBs parallel the distribution of mutations in the targeted hypermutation domain and are found preferentially at RGYW motifs, the intrinsic hot spots of somatic hypermutation. The introduction of DSBs appears to depend on transcriptional activity. Thus, secondary diversification of rearranged V gene segments relates to an error-prone nonhomologous DSB repair system acting in B cells of the GC.
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