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The H2B deubiquitinase Usp22 promotes antibody class switch recombination by facilitating non-homologous end joining

Author

Listed:
  • Conglei Li

    (University of Toronto)

  • Thergiory Irrazabal

    (University of Toronto)

  • Clare C. So

    (University of Toronto)

  • Maribel Berru

    (University of Toronto)

  • Likun Du

    (Karolinska Institutet)

  • Evelyn Lam

    (University of Toronto)

  • Alexanda K. Ling

    (University of Toronto)

  • Jennifer L. Gommerman

    (University of Toronto)

  • Qiang Pan-Hammarström

    (Karolinska Institutet)

  • Alberto Martin

    (University of Toronto)

Abstract

Class switch recombination (CSR) has a fundamental function during humoral immune response and involves the induction and subsequent repair of DNA breaks in the immunoglobulin (Ig) switch regions. Here we show the role of Usp22, the SAGA complex deubiquitinase that removes ubiquitin from H2B-K120, in the repair of programmed DNA breaks in vivo. Ablation of Usp22 in primary B cells results in defects in γH2AX and impairs the classical non-homologous end joining (c-NHEJ), affecting both V(D)J recombination and CSR. Surprisingly, Usp22 depletion causes defects in CSR to various Ig isotypes, but not IgA. We further demonstrate that IgG CSR primarily relies on c-NHEJ, whereas CSR to IgA is more reliant on the alternative end joining pathway, indicating that CSR to different isotypes involves distinct DNA repair pathways. Hence, Usp22 is the first deubiquitinase reported to regulate both V(D)J recombination and CSR in vivo by facilitating c-NHEJ.

Suggested Citation

  • Conglei Li & Thergiory Irrazabal & Clare C. So & Maribel Berru & Likun Du & Evelyn Lam & Alexanda K. Ling & Jennifer L. Gommerman & Qiang Pan-Hammarström & Alberto Martin, 2018. "The H2B deubiquitinase Usp22 promotes antibody class switch recombination by facilitating non-homologous end joining," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03455-x
    DOI: 10.1038/s41467-018-03455-x
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    Cited by:

    1. Philip Barbulescu & Chetan K. Chana & Matthew K. Wong & Ines Ben Makhlouf & Jeffrey P. Bruce & Yuqing Feng & Alexander F. A. Keszei & Cassandra Wong & Rukshana Mohamad-Ramshan & Laura C. McGary & Moha, 2024. "FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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