Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10771584 | Biochemical and Biophysical Research Communications | 2005 | 8 Pages |
Abstract
Somatic hypermutation (SHM) of immunoglobulin variable (V) region genes occurs in the germinal center (GC) B cells during immune responses, depending on activation-induced cytidine deaminase (AID). SHM is associated with resected double-strand DNA breaks (DSBs) which were shown to occur specifically in rearranged V regions in the GC B cells and CD40-stimulated B cells expressing AID. So far, endonucleases responsible for the DSBs have not been identified. Here we show that DNase γ, a member of DNase I family of endonucleases, is expressed in GC B cells and CD40-stimulated B cells. Overexpression of DNase γ in the mutation-competent Ramos B-cell line resulted in a marked increase in the resected but not blunt DSBs in the V region. Conversely, a selective DNase γ inhibitor, DR396, suppressed the generation of the resected DSBs. These results suggest that DNase γ is involved in the generation of resected DSBs associated with SHM.
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Authors
Mariko Okamoto, Noriaki Okamoto, Hisako Yashiro, Daisuke Shiokawa, Satoshi Sunaga, Atsushi Yoshimori, Sei-ichi Tanuma, Daisuke Kitamura,