Functional analysis of G-quadruplex structures and telomerase activity for DNA double strand break formation and their impact on genome integrity

• Applicant: Professorin Dr. Katrin Paeschke
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2011 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 200762257

The preservation of genomic stability is a major challenge for every cell, and is dependent on many proteins. Among these, telomerase a reverse transcriptase, maintains telomere, but has also the po-tential to interfere with DNA double strand break (DSB) repair. This de novo telomere addition could lead to loss of chromosomal arms subsequently loss of genetic information and genome stability. In genome wide analysis I identified many unexpected telomerase-binding sites, which is a strong indication, that telomerase contributes at these sites to genome instability. In aim 1 we will analyze with Chromatin Immunoprecipitation telomerase function at non-telomeric sites and determine how telomerase is recruited to these sites. In aim 2, the participation of G-quadruplexes (G4) structures for genome stability and gene regulation will be examined. During this proposal we will investigate G4 DNA structures as regulatory elements during meiosis and transcription and later connect misregulation of this structure to mutations observed during aging. Results gained from these two projects will give deep insights into DSB repair, gene regulation and the connection to genome stability.

• DFG Programme: Independent Junior Research Groups