title: Activation-induced cytosine deaminase (AID) is actively exported out of the nucleus but retained by the induction of DNA breaks.
abstract: Activation-induced cytosine deaminase (AID) is a cytosine deaminase that is critical to immunoglobulin hypermutation, class switch recombination, and gene conversion. In the context of hypermutating B cells, AID deaminates cytosine in the DNA of immunoglobulin genes, leading to the accumulation of mutations in the variable regions. However, when AID is expressed ectopically, it is a generalized mutator of G:C base pairs. Therefore, we asked whether AID may be partially regulated by an active system of nuclear export. We found that removal of a highly conserved nuclear export signal in the C terminus of AID causes accumulation of AID in the nucleus. However, a putative nuclear localization signal in the N terminus does not appear to be functional. Finally, we found that agents that induce DNA breaks caused retention of AID in the nucleus, suggesting that DNA breaks or the repair patches initiated as a result are a substrate for AID binding.
authors.affiliation: Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA.
authors.forename: Sukhdev S
authors.initials: SS
authors.lastname: Brar
authors.forename: Mary
authors.initials: M
authors.lastname: Watson
authors.forename: Marilyn
authors.initials: M
authors.lastname: Diaz
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002645:Chickens; D020552:Comet Assay; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000737:chemistry* / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007136:Immunoglobulins / Q000235:genetics; D051379:Mice; D018613:Microscopy, Confocal; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020543:Proteome; D017386:Sequence Homology, Amino Acid; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D018076:DNA, Complementary; D007136:Immunoglobulins; D020543:Proteome; D001761:Bleomycin; D006861:Hydrogen Peroxide; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase