Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

Gayan Senavirathne, Jeffrey G. Bertram, Malgorzata Jaszczur, Kathy R. Chaurasiya, Phuong Pham, Chi H. Mak, Myron F. Goodman () and David Rueda ()
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Gayan Senavirathne: Wayne State University
Jeffrey G. Bertram: University of Southern California
Malgorzata Jaszczur: University of Southern California
Kathy R. Chaurasiya: Section of Virology, Imperial College London
Phuong Pham: University of Southern California
Chi H. Mak: University of Southern California
Myron F. Goodman: University of Southern California
David Rueda: Wayne State University

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract 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 single-molecule 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 ∼5 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.

Date: 2015
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DOI: 10.1038/ncomms10209

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