Recombinational Mechanisms of Telomere Length Maintenance

Tulane University, New Orleans LA

Investigators

Abstract

Telomeres are the specialized DNA-protein structures at the ends of eukaryotic chromosomes that protect them from degradation and from being treated as broken DNA molecules. Telomeric DNA is synthesized by telomerase, an enzyme not expressed in somatic cells. In multi-cellular organisms, erosion of telomeric sequences eventually leads to senescence. Research using single-celled organisms such as baker's yeast has contributed significantly to the understanding of the basic mechanisms of telomere maintenance. A unique recombinational single-step deletion process was first described for yeast telomeres in the Lustig laboratory. This process, termed telomere rapid deletion (TRD), reduces over-elongated telomeres to the wild-type size. TRD occurs at higher frequencies in premeiotic cells, suggesting that homology search may play a mechanistic role in this mechanism. Recently, TRD has been detected in other systems. The objectives of this project are to isolate strains carrying novel mutations that affect TRD, and to characterize TRD in both vegetatively growing and meiotic cells of both wild-type and mutant strains. Knowing how telomere length is monitored would be a significant advance for this field. The PI and his collaborator in Israel will use their skills in telomere biology and recombination, respectively, both for the positive scientific ramifications and, more importantly, to foster essential international ties in the scientific community. Both communities will have the opportunity to learn new ideas and approaches from each other.