Research Interests   Mutation; DNA repair and genetic recombination

Our laboratory focuses on how organisms preserve the integrity of their genetic information. Consequently, we explore the processes of DNA repair and genetic recombination. We use yeast cells because they possess an extensive system to ward off deleterious damage to their DNA, and because they are amenable to an assortment of molecular genetic manipulations in the laboratory. In one study we are investigating the RAD52 gene that provides a poorly understood function in recombinational repair. This type of repair occurs after DNA is damaged by ionizing radiation. We have isolated rad52 mutations that render the protein product partially active. This provides insight into the many functions of the gene and has also permitted the selection of extragenic suppressor mutations that identify additional proteins that work in concert with the Rad52 protein. A second project is an examination of the factors that make repetitions of the trinucleotide CAG unstable. Tracts of CAG repeats are the cause of a number of human hereditary neurological disorders. Our studies have shown that aberrations in Okazaki fragment maturation cause CAG repeat tracts to expand and that a failure to processively polymerize through repeat tracts cause tracts to contract.

Kim H, Livingston DM. (2006). A high mobility group protein binds to long CAG repeat tracts and establishes their chromatin organization in Saccharomyces cerevisiae. J Biol Chem. 9;281(23):15735-40.

Refsland EW, Livingston DM. (2005). Interactions among DNA ligase I, the flap endonuclease and proliferating cell nuclear antigen in the expansion and contraction of CAG repeat tracts in yeast. Genetics. 171(3):923-34.

Asleson EN, Livingston DM. (2003). Investigation of the stability of yeast rad52 mutant proteins uncovers post-translational and transcriptional regulation of Rad52p. Genetics. 163(1):91-101.

Schweitzer, J.K., Reinke, S.S. and Livingston, D.M. (2001) Meiotic alterations in CAG repeat tracts. Genetics 159:1861-1865.

Ireland,M.J., Reinke, S.S. and Livingston, D.M. (2000) The impact of lagging strand replication mutations on the stability of CAG repeat tracts in yeast. Genetics 155(4):1657-65.

Asleson,E.N., Okagaki, R.J. and Livingston, D.M. (1999) A core activity associated with the N terminus of the yeast RAD52 protein is revealed by RAD51 overexpression suppression of C-terminal truncation alleles. Genetics 153:681-692.

Schweitzer, J.K. and Livingston, D.M. (1999) The effect of DNA replication mutations on CAG tract stability in yeast. Genetics 152:953-963.

Maurer, D.J., O'Callaghan, B.L. and Livingston, D.M. (1998) Mapping the polarity of changes that occur in interrupted CAG repeat tracts in yeast. Mol. Cell. Biol. 18:4597-4604.

Schweitzer, J.K. and Livingston, D.M. (1998) Expansions of CAG repeat tracts are frequent in a yeast mutant defective in Okazaki fragment maturation. Hum. Molec. Genetics 7:69-74.

Schweitzer, J.K. and Livingston, D.M. (1997) Destabilization of CAG trinucleotide repeat tracts by mismatch repair mutations in yeast. Hum. Molec. Genetics 6:349-355.

Nguyen, M.M. and Livingston, D.M. (1997) Cold sensitive rad52 alleles of yeast. Current Genetics 32:100-107.