Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand

Somatic hypermutation and class switch recombination are DNA modification reactions that alter the genes encoding antibodies in B lymphocytes. Both of these distinct reactions require activation-induced deaminase (AID) and transcription. Here we show that in Escherichia coli , as in eukaryotic cells...

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Veröffentlicht in:Nature immunology Jg. 4; H. 5; S. 452 - 456
Hauptverfasser: Ramiro, Almudena R., Stavropoulos, Pete, Jankovic, Mila, Nussenzweig, Michel C.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Nature Publishing Group US 01.05.2003
Nature Publishing Group
Schlagworte:
Animals
Base Sequence
Biomedical and Life Sciences
Biomedicine
Cytidine - metabolism
Cytidine Deaminase - metabolism
Deoxyribonucleic acid
DNA
DNA, Bacterial - chemistry
DNA, Bacterial - genetics
DNA, Bacterial - metabolism
DNA, Single-Stranded - chemistry
DNA, Single-Stranded - genetics
DNA, Single-Stranded - metabolism
E coli
Escherichia coli - genetics
Escherichia coli - metabolism
Genes, Bacterial
Humans
Immunoglobulin Class Switching
Immunology
Infectious Diseases
Lymphocytes
Models, Immunological
Molecular Sequence Data
Mutation
Plasmids - genetics
Recombination, Genetic
RNA - genetics
RNA - metabolism
Somatic Hypermutation, Immunoglobulin
Substrate Specificity
Transcription, Genetic
ISSN:1529-2908, 1529-2916
Online-Zugang:Volltext
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Beschreibung
Zusammenfassung:Somatic hypermutation and class switch recombination are DNA modification reactions that alter the genes encoding antibodies in B lymphocytes. Both of these distinct reactions require activation-induced deaminase (AID) and transcription. Here we show that in Escherichia coli , as in eukaryotic cells, the mutation frequency is directly proportional to the transcription of target genes. Transcription enhances mutation of the nontemplate DNA strand, which is exposed as single-stranded DNA during the elongation reaction, but not mutation of the template DNA strand, which is protected by E. coli RNA polymerase. Our results establish a direct link between AID and transcription and suggest that the role of transcription in facilitating mutation is to provide AID with access to single-stranded DNA.
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ISSN:1529-2908
1529-2916
DOI:10.1038/ni920