title: AID: how does it aid antibody diversity?
abstract: Activation-induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (SHM), and gene conversion (GC). AID is known to be required for DNA cleavage of S regions in CSR. However, its molecular mechanism is a focus of extensive debate. RNA editing hypothesis postulates that AID edits yet unknown mRNA to generate specific endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision repair enzymes. We discuss available evidence for the two proposed models. Recent findings, namely requirement of protein synthesis for DNA breakage and dispensability of U removal activity of uracil DNA glycosylase, force us to reconsider DNA deamination hypothesis.
authors.affiliation: Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501, Japan. honjo@mfour.med.kyoto-u.ac.jp
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Sidonia
authors.initials: S
authors.lastname: Fagarasan
mesh_terms: D000818:Animals; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D006801:Humans; D017393:RNA Editing; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase