The role of break-induced replication in large-scale expansions of (CAG)_n/(CTG)_n repeats.

ABSTRACT: Expansions of (CAG)_n/(CTG)_n trinucleotide repeats are responsible for over a dozen neuromuscular and neurodegenerative disorders. Large-scale expansions are commonly observed in human pedigrees and may be explained by iterative small-scale events such as strand slippage during replication or repair DNA synthesis. Alternatively, a distinct mechanism may lead to a large-scale repeat expansion as a single step. To distinguish between these possibilities, we developed a novel experimental system specifically tuned to analyze large-scale expansions of (CAG)_n/(CTG)_n repeats in Saccharomyces cerevisiae. The median size of repeat expansions was ∼60 triplets, although we also observed additions of more than 150 triplets. Genetic analysis revealed that Rad

SUBMITTER: Kim JC 

PROVIDER: S-EPMC5215974 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature