Abstract
Immunoglobulin H class-switch recombination (CSR) occurs between switch regions and requires transcription and activation-induced cytidine deaminase (AID). Transcription through mammalian switch regions, because of their GC-rich composition, generates stable R-loops, which provide single-stranded DNA substrates for AID. However, we show here that the Xenopus laevis switch region S(mu), which is rich in AT and not prone to form R-loops, can functionally replace a mouse switch region to mediate CSR in vivo. X. laevis S(mu)-mediated CSR occurred mostly in a region of AGCT repeats targeted by the AID-replication protein A complex when transcribed in vitro. We propose that AGCT is a primordial CSR motif that targets AID through a non-R-loop mechanism involving an AID-replication protein A complex.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Conserved Sequence / genetics*
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Cytidine Deaminase / metabolism
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DNA / metabolism
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DNA-Binding Proteins / metabolism
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Deamination
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Evolution, Molecular*
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Hybridomas / immunology
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Immunoglobulin Class Switching / genetics*
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Immunoglobulin Class Switching / immunology
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / genetics
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Immunoglobulin G / immunology
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Immunoglobulin Switch Region / genetics*
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Mice
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Molecular Sequence Data
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Mutagenesis, Site-Directed / genetics
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Recombination, Genetic / genetics*
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Replication Protein A
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Sequence Alignment
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Spleen / immunology
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Xenopus laevis / genetics
Substances
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DNA-Binding Proteins
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Immunoglobulin G
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Replication Protein A
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Rpa1 protein, mouse
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DNA
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase