Zusammenfassung
Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by
initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during
transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using singlemolecule
FRET, we show that AID binds to transcribed dsDNA and translocates
unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles,
while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an
8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random
bidirectional short slides/hops over the entire molecule while remaining bound for B5 min.
Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can
track along with RNAP during transcription and scan within stalled transcription bubbles
suggests a mechanism by which AID can initiate SHM and CSR when properly regulated,
yet when unregulated can access non-Ig genes and cause cancer
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