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Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination

Author

Listed:
  • Hong Zan

    (Immunology and Molecular Genetics, University of Texas School of Medicine, UT Health Science Center)

  • Connie Tat

    (Immunology and Molecular Genetics, University of Texas School of Medicine, UT Health Science Center)

  • Zhifang Qiu

    (Immunology and Molecular Genetics, University of Texas School of Medicine, UT Health Science Center)

  • Julia R. Taylor

    (Immunology and Molecular Genetics, University of Texas School of Medicine, UT Health Science Center)

  • Justin A. Guerrero

    (Immunology and Molecular Genetics, University of Texas School of Medicine, UT Health Science Center)

  • Tian Shen

    (Immunology and Molecular Genetics, University of Texas School of Medicine, UT Health Science Center)

  • Paolo Casali

    (Immunology and Molecular Genetics, University of Texas School of Medicine, UT Health Science Center)

Abstract

Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S–S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR. Compared with their Rad52+/+ counterparts, which display normal CSR, Rad52−/− B cells show increased CSR, fewer intra-Sμ region recombinations, no/minimal microhomologies in S–S junctions, decreased c-Myc/IgH translocations and increased Ku70/Ku86 recruitment to S-region DSB ends. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends. It also facilitates a Ku-independent DSB repair, which favours intra-S region recombination and mediates, particularly in Ku absence, inter-S–S recombination, as emphasized by the significantly greater CSR reduction in Rad52−/− versus Rad52+/+ B cells on Ku86 knockdown.

Suggested Citation

  • Hong Zan & Connie Tat & Zhifang Qiu & Julia R. Taylor & Justin A. Guerrero & Tian Shen & Paolo Casali, 2017. "Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination," Nature Communications, Nature, vol. 8(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14244
    DOI: 10.1038/ncomms14244
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    Cited by:

    1. Estelle Vincendeau & Wenming Wei & Xuefei Zhang & Cyril Planchais & Wei Yu & Hélène Lenden-Hasse & Thomas Cokelaer & Juliana Pipoli da Fonseca & Hugo Mouquet & David J. Adams & Frederick W. Alt & Step, 2022. "SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Yijiang Xu & Hang Zhou & Ginell Post & Hong Zan & Paolo Casali, 2022. "Rad52 mediates class-switch DNA recombination to IgD," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Anastasiya Kishkevich & Sanjeeta Tamang & Michael O. Nguyen & Judith Oehler & Elena Bulmaga & Christos Andreadis & Carl A. Morrow & Manisha Jalan & Fekret Osman & Matthew C. Whitby, 2022. "Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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