My laboratory has been investigating the structure and behavior of chromosome ends, or telomeres. These specialized structures are required for chromosome stability and maintenance, yet some of their features are quite dynamic. Chromosome ends are maintained by the ribonucleoprotein, telomerase, in a regulated manner. When telomerase is absent and cells divide, telomeres erode; when telomeres reach a critical length or the structure is perturbed, the cells will either cease dividing or undergo programmed cell death. Telomere binding proteins are important to structural integrity and regulation of telomere length.

In contrast to humans, Xenopus expresses abundant telomerase activity in all somatic tissues. With support from the National Science Foundation, we have isolated Xenopus genes for all the "shelterin" components as well as additional potential telomere-regulating proteins.  Ongoing investigations include:

The architecture of the Xenopus shelterin complex:  individual protein-protein interactions are being assessed using co-immunoprecipitation of epitope-tagged Xenopus shelterins following transfection of cultured cells, and the yeast two-hybrid system.

Functional conservation:  whether the Xenopus orthologs serve the same function as their human counterparts is being determined in a variety of ways, including effects on telomerase activity in vitro and in vivo, and localization in cultured cells.

Structure-function relationships: clones of each component can be subjected to deletion and mutation studies to localize key functional domains.

Many thesis students have chosen to work on aspects of this project; recent thesis titles can be found here.

Selected Publications:

View additional publications at PubMed: