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.
Okamoto
Mariko
M
Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan.
Okamoto
Noriaki
N
Yashiro
Hisako
H
Shiokawa
Daisuke
D
Sunaga
Satoshi
S
Yoshimori
Atsushi
A
Tanuma
Sei-ichi
S
Kitamura
Daisuke
D
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D012333:RNA, Messenger; D004247:DNA; D004706:Endodeoxyribonucleases; C105124:deoxyribonuclease gamma