Talk abstracts

Talk on Friday 04:45-05:00pm submitted by Harry Scott

Structural analysis of the Ccq1-Tpz1-Poz1 telomere subcomplex in fission yeast

Harry Scott (Department of Pharmacology, Case Western University)

Telomeres are nucleoprotein complexes that cap and protect the ends of all linear chromosomes. Telomeres primarily function to maintain genome stability by preventing end-to-end fusions and deleterious induction of DNA damage response pathways. To achieve this, telomere DNA is recognized and bound by a specialized, protein complex called shelterin. The shelterin complex in Schizosaccharomyces pombe assembles from a set of six proteins (Taz1, Rap1, Poz1, Ccq1, Pot1 and Tpz1) that are orthologs of the human shelterin complex. A shelterin sub-complex, comprised of Ccq1-Poz1-Tpz1 (CTP) has been demonstrated to have regulatory roles in telomere extension by bridging regions involved in binding of double- and single-stranded regions of telomere DNA. When this bridge is intact, the telomeres reside in a non-extendable state. Conversely, when the CTP interactions are destabilized, the telomeres adopt a telomerase-extendable state. The current lack of structural information regarding telomerase regulation by shelterin proteins contributes to the elusive nature of telomere homeostasis. We have used electron microscopy to solve the structure of the CTP complex. Genetically designed tags and truncations were used localize individual domains and the termini of the three proteins within the CTP complex. These data provide the first clues regarding the overall architecture of a shelterin complex.

Keywords: telomere, structure, shelterin