Functional study of the KU complex at Arabidopsis telomeres

Telomeres are nucleoprotein structures at the end of eukaryotic chromosomes. They mask chromosome ends from being recognized and processed as DNA double strand breaks by a DNA checkpoint and repair machinery. Paradoxically, several DNA repair and checkpoint complexes have been recently localized at the telomeres in yeast and mammals. The Ku70/80 heterodimer, which is essential for DNA repair through non-homologous end joining, has the most controversial role. Ku is required for proper telomere maintenance protection, but it also mediates fusions of unprotected chromosome ends. My long-term goal is to employ Arabidopsis as a higher eukaryotic model for investigating basic questions in telomere biology and genome stability. Previously, we characterized Arabidopsis mutants deficient in catalytic subunit of telomerase and Ku70. We demonstrated that Ku negatively regulates telomerase at Arabidopsis telomeres and is required for proper maintenance of telomeric C-strand. In this application, I propose a detailed analysis of the telomeric role of Ku in Arabidopsis. We will examine functional interactions between Ku, telomerase and other DNA repair complexes implicated in telomere biogenesis. In addition, to further unravel molecular interactions at Arabidopsis telomeres, a screen for novel Ku interacting proteins will be performed.

Telomeres are nucleoprotein structures at the end of eukaryotic chromosomes. They mask chromosome ends from being recognized and processed as DNA double strand breaks by a DNA checkpoint and repair machinery. Paradoxically, several DNA repair and checkpoint complexes have been recently localized at the telomeres in yeast and mammals. The Ku70/80 heterodimer, which is essential for DNA repair through non-homologous end joining, has the most controversial role. Ku is required for proper telomere maintenance protection, but it also mediates fusions of unprotected chromosome ends. My long-term goal is to employ Arabidopsis as a higher eukaryotic model for investigating basic questions in telomere biology and genome stability. Previously, we characterized Arabidopsis mutants deficient in catalytic subunit of telomerase and Ku70. We demonstrated that Ku negatively regulates telomerase at Arabidopsis telomeres and is required for proper maintenance of telomeric C-strand. In this application, I propose a detailed analysis of the telomeric role of Ku in Arabidopsis. We will examine functional interactions between Ku, telomerase and other DNA repair complexes implicated in telomere biogenesis. In addition, to further unravel molecular interactions at Arabidopsis telomeres, a screen for novel Ku interacting proteins will be performed.