The role of break-induced replication in large-scale expansions of (CAG)n/(CTG)n repeats.
Nat Struct Mol Biol
; 24(1): 55-60, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27918542
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 â¼60 triplets, although we also observed additions of more than 150 triplets. Genetic analysis revealed that Rad51, Rad52, Mre11, Pol32, Pif1, and Mus81 and/or Yen1 proteins are required for large-scale expansions, whereas proteins previously implicated in small-scale expansions are not involved. From these results, we propose a new model for large-scale expansions, which is based on the recovery of replication forks broken at (CAG)n/(CTG)n repeats via break-induced replication.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Expansão das Repetições de DNA
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Replicação do DNA
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article