Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNAs genes

  1. Benjamin JM Taylor
  2. Yee Ling Wu
  3. Cristina Rada  Is a corresponding author
  1. Medical Research Council Laboratory of Molecular Biology, United Kingdom

Abstract

Cytidine deaminases are single stranded DNA mutators diversifying antibodies and restricting viral infection. Improper access to the genome leads to translocations and mutations in B cells and contributes to the mutation landscape in cancer, such as kataegis. It remains unclear how deaminases access double stranded genomes and whether off-target mutations favor certain loci, although transcription and opportunistic access during DNA repair are thought to play a role. In yeast, AID and the catalytic domain of APOBEC3G preferentially mutate transcriptionally active genes within narrow regions, 110 base pairs in width, fixed at RNA Polymerases initiation sites. Unlike APOBEC3G, AID shows enhanced mutational preference for small RNA genes (tRNAs, snoRNAs and snRNAs) suggesting a putative role for RNA in its recruitment. We uncover the high affinity of the deaminases for the single stranded DNA exposed by initiating RNA polymerases (a DNA configuration reproduced at stalled polymerases) without a requirement for specific cofactors.

Article and author information

Author details

  1. Benjamin JM Taylor

    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Yee Ling Wu

    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Cristina Rada

    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    For correspondence
    car@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Nick J Proudfoot, University of Oxford, United Kingdom

Version history

  1. Received: June 2, 2014
  2. Accepted: September 17, 2014
  3. Accepted Manuscript published: September 19, 2014 (version 1)
  4. Version of Record published: October 10, 2014 (version 2)

Copyright

© 2014, Taylor et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Benjamin JM Taylor
  2. Yee Ling Wu
  3. Cristina Rada
(2014)
Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNAs genes
eLife 3:e03553.
https://doi.org/10.7554/eLife.03553

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https://doi.org/10.7554/eLife.03553

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