APOBEC3B cytidine deaminase targets the non-transcribed strand of tRNA genes in yeast

Publication date: Available online 21 March 2017
Source:DNA Repair
Author(s): Natalie Saini, Steven A. Roberts, Joan F. Sterling, Ewa P. Malc, Piotr A. Mieczkowski, Dmitry A. Gordenin
Variations in mutation rates across the genome have been demonstrated both in model organisms and in cancers. This phenomenon is largely driven by the damage specificity of diverse mutagens and the differences in DNA repair efficiency in given genomic contexts. Here, we demonstrate that the single-strand DNA-specific cytidine deaminase APOBEC3B (A3B) damages tRNA genes at a 1000-fold higher efficiency than other non-tRNA genomic regions in budding yeast. We found that A3B-induced lesions in tRNA genes were predominantly located on the non-transcribed strand, while no transcriptional strand bias was observed in protein coding genes. Furthermore, tRNA gene mutations were exacerbated in cells where RNaseH expression was completely abolished (Δrnh1Δrnh35). These data suggest a transcription-dependent mechanism for A3B-induced tRNA gene hypermutation.



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