Telomere Maintenance in the Dynamic Nuclear Architecture

Telomeres, the protective structures at the end of eukaryotic chromosomes, play a pivotal role in several regulatory pathways that determine the cell fate. Human telomeres consist of thousands of TTAGGG repeats organized in a peculiar compact chromatin and bound by the six-protein complex, shelterin. In germinal and embryonic stem cells, telomere length is maintained by the activity of telomerase that adds TTAGGG repeats at the 3′ ends of chromosomes. In contrast, telomerase is inactive in somatic cells, and consequently telomeres shorten at each replication cycle till they reach a critical length that triggers a DNA damage response pathway leading to cell growth arrest, a state known as replicative senescence. In this chapter, we review what is known about telomere structure and telomeric chromatin organization. We will discuss the dynamic changes of telomeres and the epigenetic and structural modifications linked to telomere shortening and the entry in replicative senescence.