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Okamoto, M. et al.

Involvement of DNase gamma in the resected double-strand DNA breaks in immunoglobulin genes.

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 gamma, a member of DNase I family of endonucleases, is expressed in GC B cells and CD40-stimulated B cells. Overexpression of DNase gamma 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 gamma inhibitor, DR396, suppressed the generation of the resected DSBs. These results suggest that DNase gamma is involved in the generation of resected DSBs associated with SHM.[1]

References

Involvement of DNase gamma in the resected double-strand DNA breaks in immunoglobulin genes. Okamoto, M., Okamoto, N., Yashiro, H., Shiokawa, D., Sunaga, S., Yoshimori, A., Tanuma, S., Kitamura, D. Biochem. Biophys. Res. Commun. (2005) [Pubmed]

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