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Prof Bob Lahue

Professor of Molecular Genetics
SFI Principal Investigator

Research interests

  • DNA mutagenesis and repair
  • Trinucleotide repeat instability

Research overview

Our chromosomes constantly undergo the opposing forces of DNA mutagenesis and DNA repair. The balance between these two forces determines the genetic fate of our cells. Normally, DNA repair wins and our genome is kept healthy. If DNA repair fails, mutagenesis ensues, often with detrimental health effects.

One enigmatic exception is DNA containing trinucleotide repeats. Mutagenesis is incredibly frequent at trinucleotide repeats in families with certain hereditary neurological diseases. These site-specific expansions, or gains of triplet repeats, occur in cells that appear otherwise normal.

These features suggest that the usual rules governing mutagenesis and repair no longer apply, and that protein activities are altered when acting at triplet repeats.

We use the budding yeast Saccharomyces cerevisiae and tissue culture cells derived from human brain (fig 1) to study the genetic mechanisms of mutagenesis and repair at trinucleotide repeats.

We continue to identify yeast proteins that either inhibit or promote triplet repeat expansions, using genetic and biochemical approaches.

Once known, we look at human homologs of these yeast proteins to see if they function analogously in cultured cells of the human CNS.

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Selected publications

  • Debacker K, Frizzell A, Gleeson O, Kirkham-McCarthy L, Mertz T, Lahue RS, Histone deacetylase complexes promote trinucleotide repeat expansions. PLoS Biol 10: e1001257 (2012)
  • Gannon AM, Frizzell A, Healy E, Lahue RS, MutSbeta and histone deacetylase complexes promote expansions of trinucleotide repeats in human cells. Nucleic Acids Res 40: 10324-10333 (2012)
  • Lahue RS, Frizzell A, Histone deacetylase complexes as caretakers of genome stability. Epigenetics 7: 806-810 (2012)