RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells.
Antibody diversification by somatic hypermutation, gene conversion, and class switch recombination is completely dependent on activation-induced cytidine deaminase (AID). A recent report showing induction of DNA mutations in Escherichia coli by overexpression of AID, Apobec-1, and related members of the RNA-editing cytidine deaminase family suggested that they may directly modify deoxycytidine in DNA in mammalian cells (DNA-editing model). We therefore examined whether Apobec-1 bona fide RNA-editing enzyme could show somatic hypermutation and class switching activities in murine B lymphocytes and fibroblasts. Unlike AID, Apobec-1 was unable to induce somatic hypermutation or class switching. The results force a reevaluation of the physiological significance of the DNA deaminase activities of AID and Apobec-1 in E. coli and in vitro.
Eto
Tomonori
T
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Kinoshita
Kazuo
K
Yoshikawa
Kiyotsugu
K
Muramatsu
Masamichi
M
Honjo
Tasuku
T
D016475:3T3 Cells; D000071479:APOBEC-1 Deaminase; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D003564:Cytidine Deaminase / Q000235:genetics* / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008322:Mammals; D051379:Mice; D016296:Mutagenesis; D017393:RNA Editing / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic
D001055:Apolipoproteins B; D008164:Luminescent Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase