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A source of the single-stranded DNA substrate for activation-induced deaminase during somatic hypermutation

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  • Xiaohua Wang

    (Albert Einstein College of Medicine)

  • Manxia Fan

    (Albert Einstein College of Medicine)

  • Susan Kalis

    (Albert Einstein College of Medicine)

  • Lirong Wei

    (Albert Einstein College of Medicine)

  • Matthew D. Scharff

    (Albert Einstein College of Medicine)

Abstract

During somatic hypermutation (SHM), activation-induced deaminase (AID) mutates deoxycytidine on single-stranded DNA (ssDNA) generated by the transcription machinery, but the detailed mechanism remains unclear. Here we report a higher abundance of RNA polymerase II (Pol II) at the immunoglobulin heavy-chain variable (Igh-V) region compared with the constant region and partially transcribed Igh RNAs, suggesting a slower Pol II progression at Igh-V that could result in some early/premature transcription termination after prolonged pausing/stalling of Pol II. Knocking down RNA–exosome complexes, which could decrease premature transcription termination, leads to decreased SHM. Knocking down Spt5, which can augment premature transcription termination, leads to increase in both, SHM and the abundance of ssDNA substrates. Collectively, our data support the model that, following the reduction of Pol II progression (pausing or stalling) at the Igh-V, additional steps such as premature transcription termination are involved in providing ssDNA substrates for AID during SHM.

Suggested Citation

  • Xiaohua Wang & Manxia Fan & Susan Kalis & Lirong Wei & Matthew D. Scharff, 2014. "A source of the single-stranded DNA substrate for activation-induced deaminase during somatic hypermutation," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5137
    DOI: 10.1038/ncomms5137
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