Poster abstracts
Poster number 127 submitted by Jens Schmidt
Mechanism of processive telomerase catalysis revealed by high-resolution optical tweezers
Eric M. Patrick (Institute for Quantitative Health Sciences and Engineering, Michigan State University, East Lansing, MI), Joseph Slivka, Bramyn Payne, Matthew J. Comstock (Department of Physics and Astronomy, Michigan State University, East Lansing MI), Jens C. Schmidt (Institute for Quantitative Health Sciences and Engineering, Department of Physics and Astronomy, Michigan State University, East Lansing MI)
Abstract:
Telomere maintenance by telomerase is essential for continuous proliferation of human cells and is vital for the survival of stem cells and 90% of cancer cells. To compensate for telomeric DNA lost during DNA replication, telomerase processively adds GGTTAG repeats to chromosome ends by copying the template region within its RNA subunit. Between repeat additions, the RNA template must be recycled. How telomerase remains associated with substrate DNA during this critical translocation step remains unknown. Using a newly developed single-molecule telomerase activity assay utilizing high-resolution optical tweezers, we demonstrate that stable substrate DNA binding at an anchor site within telomerase facilitates the processive synthesis of telomeric repeats. After release of multiple telomeric repeats from telomerase, we observed folding of product DNA into G-quadruplex structures. Our results provide detailed mechanistic insights into telomerase catalysis, a process of critical importance in aging and cancer.
Keywords: Telomerase catalysis, optical tweezers