Recombinogenic Phenotype of Human Activation-Induced Cytosine Deaminase

Vladimir P. Poltoratsky, Samuel H. Wilson, Thomas A. Kunkel, Youri I Pavlov

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Class switch recombination, gene conversion, and somatic hypermutation that diversify rearranged Ig genes to produce various classes of high affinity Abs are dependent on the enzyme activation-induced cytosine deaminase (AID). Evidence suggests that somatic hypermutation is due to error-prone DNA repair that is initiated by AID-mediated deamination of cytosine in DNA, whereas the mechanism by which AID controls recombination remains to be elucidated. In this study, using a yeast model system, we have observed AID-dependent recombination. Expression of human AID in wild-type yeast is mutagenic for G-C to A-T transitions, and as expected, this mutagenesis is increased upon inactivation of uracil-DNA glycosylase. AID expression also strongly induces intragenic mitotic recombination, but only in a strain possessing uracil-DNA glycosylase. Thus, the initial step of base excision repair is required for AID-dependent recombination and is a branch point for either hypermutagenesis or recombination.

Original languageEnglish (US)
Pages (from-to)4308-4313
Number of pages6
JournalJournal of Immunology
Volume172
Issue number7
DOIs
StatePublished - Apr 1 2004

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Cytosine Deaminase
Genetic Recombination
Phenotype
Uracil-DNA Glycosidase
DNA Repair
Yeasts
Switch Genes
Gene Conversion
Immunoglobulin Genes
Deamination
Enzyme Activation
Cytosine
AICDA (activation-induced cytidine deaminase)
Mutagenesis
DNA

ASJC Scopus subject areas

  • Immunology

Cite this

Recombinogenic Phenotype of Human Activation-Induced Cytosine Deaminase. / Poltoratsky, Vladimir P.; Wilson, Samuel H.; Kunkel, Thomas A.; Pavlov, Youri I.

In: Journal of Immunology, Vol. 172, No. 7, 01.04.2004, p. 4308-4313.

Research output: Contribution to journalArticle

Poltoratsky, Vladimir P. ; Wilson, Samuel H. ; Kunkel, Thomas A. ; Pavlov, Youri I. / Recombinogenic Phenotype of Human Activation-Induced Cytosine Deaminase. In: Journal of Immunology. 2004 ; Vol. 172, No. 7. pp. 4308-4313.
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