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.