title: APOBEC3B can impair genomic stability by inducing base substitutions in genomic DNA in human cells.
abstract: Human APOBEC3 proteins play pivotal roles in intracellular defense against viral infection by catalyzing deamination of cytidine residues, leading to base substitutions in viral DNA. Activation-induced cytidine deaminase (AID), another member of the APOBEC family, is capable of editing immunoglobulin (Ig) and non-Ig genes, and aberrant expression of AID leads to tumorigenesis. However, it remains unclear whether APOBEC3 (A3) proteins affect stability of human genome. Here we demonstrate that both A3A and A3B can induce base substitutions into human genome as AID can. A3B is highly expressed in several lymphoma cells and somatic mutations occur in some oncogenes of the cells highly expressing A3B. Furthermore, transfection of A3B gene into lymphoma cells induces base substitutions in cMYC gene. These data suggest that aberrant expression of A3B can evoke genomic instability by inducing base substitutions into human genome, which might lead to tumorigenesis in human cells.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shinohara
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Io
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shindo
authors.forename: Masashi
authors.initials: M
authors.lastname: Matsui
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Tada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Kadowaki
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015894:Genome, Human; D042822:Genomic Instability; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D015778:Minor Histocompatibility Antigens; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase