ena-STUDY-MRC LABORATORY OF MOLECULAR BIOLOGY, CAMBRIDGE-06-10-2014-15:30:36:316-797
Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes
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.
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.