AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts.
Activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is indispensable for somatic hypermutation (SHM), class switch recombination, and gene conversion of immunoglobulin genes, which indicates a common molecular mechanism for these phenomena. Here we show that ectopic expression of AID alone can induce hypermutation in an artificial GFP substrate in NIH 3T3 murine fibroblast cells. The frequency of mutations was closely correlated with the level of transcription of the target gene, and the distribution of mutations in NIH 3T3 cells was similar to those of SHM in B lymphocytes. These results indicate that AID is sufficient for the generation of SHM in an actively transcribed gene in fibroblasts, as well as B cells, and that any of the required cofactors must be present in these fibroblasts.
Yoshikawa
Kiyotsugu
K
Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Okazaki
Il-Mi
IM
Eto
Tomonori
T
Kinoshita
Kazuo
K
Muramatsu
Masamichi
M
Nagaoka
Hitoshi
H
Honjo
Tasuku
T
D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011994:Recombinant Proteins / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin; D014158:Transcription, Genetic; D014162:Transfection; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase