Mechanisms of chromosome end protection.

Telomeres form the ends of eukaryotic chromosome and are essential for genome stability and its complete replication. Loss of telomere function may result in activation of apoptosis and cellular senescence and telomere metabolism plays an important role in human aging and tumor suppression. The fundamental question in telomere biology is how telomeres protect natural chromosome ends from being recognized as DNA damage. In this project we tried to address this question using Arabidopsis thaliana as a model organism. We discovered a novel mechanism of chromosome end protection that does not rely on single stranded DNA that usually forms ends of telomeres. Instead, we found that a fraction of plant telomeres are blunt-ended and their protection requires DNA repair complex Ku. We examined how Ku protects telomeres and proposed a model according to which is terminal telomere structure determined by its mode of replication. We gained support for this model by analyzing telomeres in plants deficient in DNA replication factors. Furthermore, we found that STN1, a protein known for its function in telomere protection and replication, plays a role in DNA synthesis at non-telomeric loci. Another interesting outcome of this project was determination of a minimal amount of telomeric DNA required for telomere function. We also explored vast genetic resources available in A. thaliana to dissect genetic architecture of telomere length variation in natural populations.