Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNAs genes
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.
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Reviewing Editor
- Nick J Proudfoot, University of Oxford, United Kingdom
Version history
- Received: June 2, 2014
- Accepted: September 17, 2014
- Accepted Manuscript published: September 19, 2014 (version 1)
- 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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