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Open Access Green as soon as Postprint is submitted to ZB.
Possible contribution of DNase γ to immunoglobulin V gene diversification.
Immunol. Lett. 125, 22-30 (2009)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Somatic hypermutation; Immunoglobulin variable region; Double-strand DNA breaks; Endonucleases; DNase gamma; class switch recombination; single-stranded-dna; cytidine deaminase aid; somatic hypermutation; cell-line; homologous recombination; antibody diversity; breaks; conversion; translocations
ISSN (print) / ISBN
0165-2478
e-ISSN
1879-0542
Journal
Immunology Letters
Quellenangaben
Volume: 125,
Issue: 1,
Pages: 22-30
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Radiation Biology (IMS)