Trinucleotide repeat expansions cause more than 30 severe neuromuscular and neurodegenerative disorders, including Huntington’s disease, myotonic dystrophy type 1, and fragile X syndrome. Although the MMR system is well known for its role in maintaining replication fidelity, key MMR proteins, especially MutSβ, have been implicated in promoting trinucleotide repeat instability. However, the molecular basis by which the MMR system causes trinucleotide repeat expansions is not known.
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