Repeat expansions are thought to involve slipped-strand DNAs as mutagenic intermediates formed during DNA replication, DNA damage (strand breaks) and recombination. We demonstrated that trinucleotide repeats can easily form slipped-strand DNA structures. These intermediates have long been suspected to escape repair. Using an in vitro repair assay recently developed in the laboratory, we can study the repair mechanism of slipped-DNA substrates containing an excess of CAG or CTG repeats as well as any human proteins that may be involved. Surprisingly, slipped DNAs are processed in a complex manner that can further contribute to mutations. Slipped CGG/CCG repeats are also being studied. Other aspects of repair involve understanding tissue-specific somatic mutations, as arise in patient muscle and neurons.