title: Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein.
abstract: The activation induced cytidine deaminase (AID) protein is known to initiate somatic hypermutation, gene conversion or switch recombination by cytidine deamination within the immunoglobulin loci. Using chromosomally integrated fluorescence reporter transgenes, we demonstrate a new recombinogenic activity of AID leading to intra- and intergenic deletions via homologous recombination of sequence repeats. Repeat recombination occurs at high frequencies even when the homologous sequences are hundreds of bases away from the positions of AID-mediated cytidine deamination, suggesting DNA end resection before strand invasion. Analysis of recombinants between homeologous repeats yielded evidence for heteroduplex formation and preferential migration of the Holliday junctions to the boundaries of sequence homology. These findings broaden the target and off-target mutagenic potential of AID and establish a novel system to study induced homologous recombination in vertebrate cells.DOI: http://dx.doi.org/10.7554/eLife.03110.001.
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland brstdd@googlemail.com.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Buerstedde
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Noel
authors.initials: N
authors.lastname: Lowndes
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, United States Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Schatz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D003434:Crossing Over, Genetic; D003564:Cytidine Deaminase / Q000378:metabolism*; D005785:Gene Conversion; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D059765:Homologous Recombination; D006801:Humans; D007134:Immunoglobulin Switch Region; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D059767:Recombinational DNA Repair; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D027041:Somatic Hypermutation, Immunoglobulin; D000097573:Red Fluorescent Protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D003564:Cytidine Deaminase; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009692:Nucleic Acid Heteroduplexes; D000097573:Red Fluorescent Protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
keywords: AID; DNA repair; homologous recombination