Effects of mutant cdc13 on CAG repeat fragility and instability in Saccharomyces cerevisiae.
Molina Vargas, Adrian Moises.
2018
- Repetitive DNA sequences break at a higher frequency than non-repetitive DNA sequences. In addition, the repetitive sequences are unstable, and can undergo expansions and contractions. Trinucleotide repeats are a category of repetitive DNA elements that can form secondary structures and cause many diseases. For example, expansions of (CAG)n/(CTG)n trinucleotide repeats are responsible for many ... read moreneuromuscular and neurodegenerative disorders like Huntington’s disease, myotonic dystrophy, and several spinocerebellar ataxias. The Cdc13 protein is a RPA-like protein that binds to the telomeric overhang and it is the main component of the CST complex, responsible for chromosome end capping and telomere length regulation. Recent evidence suggested that Cdc13 might protect against GAA repeat expansions. In this study, the well-characterized temperature-sensitive cdc13-1 mutation was introduced in several assay systems in S. cerevisiae to study instability and fragility within CAG/CTG repeats. We have found increased rates of chromosome breakage in mutants grown at a semi-permissive temperature. Regarding instability, it was seen that a dysfunctional Cdc13 protein produces a contraction-prone phenotype. When selecting for large-scale CAG expansions, we observed signs of an increased rate of expansion or mutation of the selectable cassette. While further research must be done in this topic, the evidence presented here supports the hypothesis that Cdc13 might be able to protect against CAG instability and fragility by binding to these repetitive sequences when exposed as ssDNA.read less
- ID:
- t148fv03n
- Component ID:
- tufts:sd.0000775
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