Nat Immunol. December 1, 2004; 5 (12): 1275-81.

An evolutionarily conserved target motif for immunoglobulin class-switch recombination.

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.

PubMed ID: 15531884
Article link: Nat Immunol.
Grant support: AI07512 NIAID NIH HHS , AI31541 NIAID NIH HHS

Genes referenced: cda


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