Catherine Freudenreich

Accepting post-doctoral applicants through Tufts IRACDA program
Area: Replication and Repair of Structure-forming DNA and Consequences for Genome Stability
Email cover letter to: Catherine.Freudenreich@tufts.edu

• PhD, Duke University, 1994

Genetics and Molecular Biology. Genome instability, particularly at sites of repetitive and structure-forming DNA

Graduate Research Area: Genetics and Molecular Biology

My lab uses the yeast, Saccharomyces cerevisiae (baker's yeast) as a model organism to study how genome instability contributes to human genetic disease. The majority of inherited genetic diseases are caused by point mutations in DNA. However, in 1991, a new type of mutation was discovered: the expansion of trinucleotide repeat sequences. This type of mutation, expansion of a repetitive DNA sequence, is the cause of a number of inherited diseases. Some examples include Huntington's disease (a degenerative neurological disease), Fragile X syndrome (the most common inherited mental retardation), and myotonic dystrophy (a type of muscular dystrophy).

The mechanism of trinucleotide repeat instability is interesting both for understanding the origin of the triplet repeat diseases and for a basic understanding of genome stability in humans. The timing and mechanism of expansion are important for understanding how triplet diseases are inherited, as well as for predicting disease development during an individual's lifetime. In addition, expanded CGG/CCG and CTG/CAG sequences are sites of chromosome fragility, areas prone to breakage in vivo. Chromosome breakage is implicated in the generation of translocations and deletions found in many types of cancer. One aim of my lab is to elucidate the mechanisms involved in triplet repeat instability and fragility, and determine how these two unusual characteristics are interrelated. For example, we are analyzing tract stability and fragility in yeast mutants deficient in processes important for genome stability such as DNA replication, DNA repair, and the cell cycle checkpoint. To find other pathways involved in repeat instability, we are using a novel genetic assay to screen for proteins whose expression influences repeat expansion or fragility. In addition to triplet repeats, several other types of minisatellite sequences that act as fragile sites have been characterized in human cells, and we are testing whether the conditions and proteins that affect triplet repeats also affect these sequences, and the consequences of chromosome breakage for cell growth and survival.