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

Author

Listed:
  • 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
    Single Molecule Imaging Group, MRC Clinical Sciences Center, Imperial College London)

  • Phuong Pham

    (University of Southern California)

  • Chi H. Mak

    (University of Southern California
    Center for Applied Mathematical Science, University of Southern California)

  • Myron F. Goodman

    (University of Southern California
    University of Southern California)

  • David Rueda

    (Wayne State University
    Section of Virology, Imperial College London
    Single Molecule Imaging Group, MRC Clinical Sciences Center, Imperial College London)

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.

Suggested Citation

  • Gayan Senavirathne & Jeffrey G. Bertram & Malgorzata Jaszczur & Kathy R. Chaurasiya & Phuong Pham & Chi H. Mak & Myron F. Goodman & David Rueda, 2015. "Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10209
    DOI: 10.1038/ncomms10209
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