department of pharmacology

Taylor Laboratory

Telomeres/Telomerase: Macromolecular Assemblies



telomere

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Telomeres are specialized structures that cap and protect the ends of chromosomes. Telomeric DNA is composed of a repeating hexameric sequence (5’-TTAGGG-3’ in humans) that terminates in a 3’ single stranded overhang. The telomeric DNA is protected from events normally signaled by an unprotected DNA end, such as fusion and DNA repair and degradation, by six proteins that form a multi-meric complex called shelterin. Due to an event called the end-replication problem, DNA polymerases are unable to fully replicate the extreme ends of chromosomal DNA before cell division. To compensate for this loss, replication of telomeric DNA is maintained by a unique macromolecular assembly called telomerase. Telomerase is another multi-component, ribonucleoprotein complex, comprised of a reverse-transcriptase motif, a large RNA molecule, and several accessory proteins. The processes of telomeric extension, maintenance, and regulation reside in a delicate balance of intimate interactions that occur between the telomere and telomerase. Under-activity of telomerase leads to progressive attrition of telomeres, which accelerates cellular and organismal aging. Conversely, telomerase hyper-activity is a hallmark of cancer cells and leads to an increased incidence of tumor formation. My lab is working to determine the three-dimensional structures of telomere and telomerase complexes to better understand the intricate function and regulation of these two macromolecular assemblies and their respective role in maintaining chromosome length and homeostasis.