title: Molecular mechanism of class switch recombination: linkage with somatic hypermutation.
abstract: Class switch recombination (CSR) and somatic hypermutation (SHM) have been considered to be mediated by different molecular mechanisms because both target DNAs and DNA modification products are quite distinct. However, involvement of activation-induced cytidine deaminase (AID) in both CSR and SHM has revealed that the two genetic alteration mechanisms are surprisingly similar. Accumulating data led us to propose the following scenario: AID is likely to be an RNA editing enzyme that modifies an unknown pre-mRNA to generate mRNA encoding a nicking endonuclease specific to the stem-loop structure. Transcription of the S and V regions, which contain palindromic sequences, leads to transient denaturation, forming the stem-loop structure that is cleaved by the AID-regulated endonuclease. Cleaved single-strand tails will be processed by error-prone DNA polymerase-mediated gap-filling or exonuclease-mediated resection. Mismatched bases will be corrected or fixed by mismatch repair enzymes. CSR ends are then ligated by the NHEJ system while SHM nicks are repaired by another ligation system.
authors.affiliation: Department of Medical Chemistry, 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: Kazuo
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch; D003564:Cytidine Deaminase / Q000378:metabolism; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004260:DNA Repair; D005812:Genes, Switch; D008040:Genetic Linkage; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D017393:RNA Editing; D045522:Recombinases; D011995:Recombination, Genetic
chemical_list: D045522:Recombinases; D004254:DNA Nucleotidyltransferases; D003564:Cytidine Deaminase