title: Involvement of DNase gamma in the resected double-strand DNA breaks in immunoglobulin genes.
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 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.
authors.affiliation: Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Okamoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Okamoto
authors.forename: Hisako
authors.initials: H
authors.lastname: Yashiro
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shiokawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sunaga
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshimori
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Tanuma
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D004247:DNA; D004706:Endodeoxyribonucleases; C105124:deoxyribonuclease gamma