Bob Lahue

Prof Bob Lahue

Professor in Biochemistry
bob.lahue@universityofgalway.ie

Research interests

DNA mutagenesis
DNA Repair
Trinucleotide Repeat Instability

Research overview

Our chromosomes constantly undergo the opposing forces of DNA mutagenesis and DNA repair. 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 genetics, biochemistry and cell biology to study triplet repeat expansions in cultured cells of the human central nervous system. The goal of this work is to uncover the molecular mechanisms of how triplet repeats expand, and what protein factors are important in favoring or inhibiting the expansion process.

To date, the mismatch repair protein MutSß and the histone deacetylases HDAC3 and HDAC5 were identified as key factors that favor expansions. Their activities are counteracted by the DNA helicase RTEL1, which inhibits expansions. The activities of these proteins are currently under active investigation.