Structure of Telomerase RNA and telomeric proteins
EMSL Project ID
2574a
Abstract
Telomerase is the ribonucleoprotein (RNP) enzyme responsible in most eukaryotes for the replication of the chromosome termini (telomeres). It is composed of an RNA (of 400 nucleotides in vertebrates) and several proteins that associate with it and carry out the enzymatic activity of the holoenzyme and also promote its cellular localization and assembly. The RNA is a landing pad to allow protein binding, but it also performs essential functions in regulating the unusual processivity of telomerase and other properties of this enzyme. Since telomerase is selectively activated in most human cancers, its inhibition could provide new antineoplastic agents with broad activity. Despite its importance, there are at the moment only a few high-resolution structures from NMR for the protein components of telomerase or the essential structural domains of its RNA component. This is a critical limiting point in efforts directed at addressing the biological function of this enzyme and at devising new ways to inhibit its function in transformed cells. We aim to obtain the structure of critical domains of telomerase RNA and of the proteins that interact with such domains. Success in this project would provide much deeper insight into the enzyme’s biological function and would allow rational methods to be applied to the design of new inhibitors that regulate its activity.
Project Details
Project type
Capability Research
Start Date
2004-04-30
End Date
2004-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members