APOBEC3A deaminates CTG hairpin loops to promote fragility and instability of expanded CAG/CTG repeats.

ABSTRACT: CAG/CTG repeats are prone to expansion, causing several inherited human diseases. The initiating sources of DNA damage which lead to inaccurate repair of the repeat tract to cause expansions are not fully understood. Expansion-prone CAG/CTG repeats are actively transcribed and prone to forming stable R-loops with hairpin structures forming on the displaced single-stranded DNA (S-loops). We previously determined that damage by the Saccharomyces cerevisiae cytosine deaminase, Fcy1, was required for both fragility and instability of CAG/CTG tracts engaged in R-loops. To determine whether this mechanism is more universal, we expressed human cytidine deaminases APOBEC3A (A3A), APOBEC3B (A3B), or activation-induced cytidine deaminase (AID) in our yeast system. We show that mutageni

SUBMITTER: Brown RE 

PROVIDER: S-EPMC11745325 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature