Possible contribution of DNase gamma to immunoglobulin V gene diversification.
Somatic hypermutation (SHM) diversifies the rearranged immunoglobulin variable (V) region gene in B cells, contributing to affinity maturation of antibodies. It is believed that SHM is generated either by direct replication or by error-prone repair systems resolving V region DNA lesions caused directly or indirectly by cytidine deaminase AID. In accord with a part of these mechanisms, it was reported that SHM is associated with staggered double-strand DNA breaks (DSBs) occurring in the rearranged V regions. However, endonucleases responsible for the DSBs remain elusive. Here we show that DNase gamma, a member of DNase I family endonucleases, contributes to the generation of SHM including point mutation, and nucleotide insertion and deletion in chicken DT40 B cell line. DNase gamma also contributes to the generation of staggered DSBs in the rearranged V region. These results raise a possibility that DNase gamma is involved in the V gene mutation machinery.
Okamoto
Noriaki
N
Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Okamoto
Mariko
M
Araki
Shinsuke
S
Arakawa
Hiroshi
H
Mizuta
Ryushin
R
Kitamura
Daisuke
D
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D004247:DNA / Q000276:immunology / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D009154:Mutation; D027041:Somatic Hypermutation, Immunoglobulin
D007135:Immunoglobulin Variable Region; D004247:DNA; D004706:Endodeoxyribonucleases; C105124:deoxyribonuclease gamma