Functions and regulation of DNA repair activities at eukaryotic chromosome ends: impact and consequences for genome stability

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The protection and faithful transmission of genetic information is essential for adequate cell function and survival. The physical ends of linear eukaryotic chromosomes, called telomeres, are complex nucleoprotein structures essential for the stability and integrity of the eukaryotic genome. Telomeres fulfill two important functions: first, they assure complete replication of chromosome termini and, second, they distinguish chromosomal ends from DNA double stranded breaks (DSB), a type of highly toxic DNA lesions. DSB are readily detected by cellular surveillance mechanisms that arrest cell cycle progression and channel them to DNA repair machinery. In contrast to DSB, chromosomal ends must be hidden form DNA repair activities. Repair transactions at telomeres can lead to loss of genetic information, genome instability, cellular transformation and, ultimately, cell death. Paradoxically, factors involved in DSB sensing and repair associate with telomeres and assist in telomere maintenance. However, it is unclear how the routine DNA repair functions of these factors are regulated at telomeres.