SUNY at Albany
June 19-23, 2001
Biochemical and Structural Investigation of the Sequence-Specific Binding Interaction between the Yeast Protein Cdc13p and Single-Stranded Telomeric DNA
Telomeres, the nucleoprotein complexes at the end of linear, eukaryotic chromosomes, protect chromosomes from degradation and end-to-end fusion and mediate the proliferative lifetime of the cell. These functions implicate telomere maintenance in cancer, as well as in the cellular aging process. Telomeric DNA is composed of a non-coding, repetitive sequence, which ends in a single-stranded TG-rich overhang. In the model organism Saccharomyces cerevisiae, the telomeric sequence is TG1-3. The essential yeast protein Cdc13p is required for both telomere replication and protection of chromosome ends from degradation. Cdc13p binds the single-stranded S. cerevisiae telomeric overhangs with high affinity (Kd=0.3 nM) and sequence specificity. We have identified an independent Cdc13p domain which retains full ssDNA binding activity and are currently using both biochemical and structural methods to study the determinants of interaction between the isolated domain and single-stranded telomeric DNA.
Deborah S. Wuttke
University of Colorado at Boulder,