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A licensing step links AID to transcription elongation for mutagenesis in B cells

Author

Listed:
  • Stephen P. Methot

    (Institut de Recherches Cliniques de Montréal
    McGill University
    Friedrich Miescher Institute for Biomedical Research)

  • Ludivine C. Litzler

    (Institut de Recherches Cliniques de Montréal
    2900 boul.)

  • Poorani Ganesh Subramani

    (Institut de Recherches Cliniques de Montréal
    McGill University)

  • Anil K. Eranki

    (Institut de Recherches Cliniques de Montréal)

  • Heather Fifield

    (Memorial University of Newfoundland)

  • Anne-Marie Patenaude

    (Institut de Recherches Cliniques de Montréal
    Genos BioCentar Borongajska cesta 83H)

  • Julian C. Gilmore

    (Institut de Recherches Cliniques de Montréal)

  • Gabriel E. Santiago

    (University of Miami)

  • Halil Bagci

    (Institut de Recherches Cliniques de Montréal
    McGill University)

  • Jean-François Côté

    (Institut de Recherches Cliniques de Montréal
    McGill University
    Université de Montréal)

  • Mani Larijani

    (Memorial University of Newfoundland)

  • Ramiro E. Verdun

    (University of Miami
    Miami Veterans Affairs Healthcare System)

  • Javier M. Di Noia

    (Institut de Recherches Cliniques de Montréal
    McGill University
    2900 boul.
    Université de Montréal)

Abstract

Activation-induced deaminase (AID) mutates the immunoglobulin (Ig) genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, thus underpinning antibody responses. AID mutates a few hundred other loci, but most AID-occupied genes are spared. The mechanisms underlying productive deamination versus non-productive AID targeting are unclear. Here we show that three clustered arginine residues define a functional AID domain required for SHM, CSR, and off-target activity in B cells without affecting AID deaminase activity or Escherichia coli mutagenesis. Both wt AID and mutants with single amino acid replacements in this domain broadly associate with Spt5 and chromatin and occupy the promoter of AID target genes. However, mutant AID fails to occupy the corresponding gene bodies and loses association with transcription elongation factors. Thus AID mutagenic activity is determined not by locus occupancy but by a licensing mechanism, which couples AID to transcription elongation.

Suggested Citation

  • Stephen P. Methot & Ludivine C. Litzler & Poorani Ganesh Subramani & Anil K. Eranki & Heather Fifield & Anne-Marie Patenaude & Julian C. Gilmore & Gabriel E. Santiago & Halil Bagci & Jean-François Côt, 2018. "A licensing step links AID to transcription elongation for mutagenesis in B cells," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03387-6
    DOI: 10.1038/s41467-018-03387-6
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