Activation-induced Cytosine Deaminase (AID) Is Actively Exported out of the Nucleus but Retained by the Induction of DNA Breaks

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 m...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-06, Vol.279 (25), p.26395-26401
Main Authors: Brar, Sukhdev S., Watson, Mary, Diaz, Marilyn
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Amino Acid Sequence
Animals
Bleomycin - pharmacology
Cell Line
Cell Nucleus - metabolism
Chickens
Comet Assay
Cytidine Deaminase
Cytosine Deaminase - chemistry
Cytosine Deaminase - metabolism
DNA Damage
DNA Repair
DNA, Complementary - metabolism
Flow Cytometry
Gamma Rays
Humans
Hydrogen Peroxide - pharmacology
Immunoglobulins - genetics
Mice
Microscopy, Confocal
Models, Biological
Molecular Sequence Data
Mutation
Plasmids - metabolism
Protein Binding
Protein Structure, Tertiary
Protein Transport
Proteome
Sequence Homology, Amino Acid
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M403503200