Regulating telomere structure and telomerase recruitment

• Applicant: Professor Dr. Hans Joachim Lipps
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2006 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 28382259

It has been well demonstrated that the macronuclear telomeres of stichotrichous ciliates adopt the antiparallel G-quadruplex structure in vivo and adopt this structure while bound via the asubunit of the telomere end-binding protein (TEBP) to a subnuclear structure, possibly the nuclear matrix or scaffold. In the course of replication, both, the interaction of telomeres as well as G-quadruplex structure become resolved. One scope of this proposal is to analyze how G-quadruplex DNA structure becomes resolved during replication in a timely manner in these cells, to identify the TEBPot interaction panner in the subnuclear structure and to analyze how this interaction is resolved during replication. For this we will analyze the phosphorylation status of TEBPß during replication and how this contributes to the resolution of G-quadruplex structure in vitro and in vivo. The fate of TEBPa during replication will be determined and a possible contribution of telomerase in the resolution of G-quadruplex structure tested. The interaction partner to which TEBPa tethers telomeres can be identified either by a modified Western analysis or chromatin immunoprecipttation and its possible modification during S-phase will be tested in vitro and in vivo. Although it is generally assumed that mammalian telomeres adopt the T-loop structure m vivo there is increasing indirect evidence that they may also adopt G-quadruplex structure. Using the same approach as successfully applied in ciliates we will make an attempt to test whether mammalian telomeres adopt G-quadruplex structures in vivo and how this structure may be formed by mammalian homologs to the ciliate TEBP. This is the second scope of this proposal and, if successful, this would open up a whole novel area of research.

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Participating Person: Professorin Dr. Daniela Rhodes