Telomeres: Structure and Function

Telomeres are specialized, highly conserved DNA-protein complexes at the ends of linear eukaryotic chromosomes. Human telomeric DNA is composed of tandem repeats of the sequence 5′-(TTAGGG)n-3′ and is complexed with sequence-specific DNA binding proteins, forming a distinctive "cap" at the ends of chromosomes. Telomeres serve to distinguish the end of the chromosome from an internal DNA break and the cellular DNA repair machinery, thereby protecting chromosomes from deleterious end-to-end fusions. Telomeres are dynamic structures, shortening during each cycle of DNA replication and cell division. In the absence of a compensatory telomere-lengthening mechanism, progressive telomere shortening imposes limits on the proliferative capacity of cells, contributing to organismal aging. Cells with unlimited proliferative capacity – notably stem cells and cancer cells – must activate a telomere lengthening mechanism. There are two such mechanisms known in humans: the ribonucleoprotein enzyme telomerase (discussed in Chap. Telomerase) and the recombination-based mechanism Alternative Lengthening of Telomeres. Most human somatic cells do not maintain their telomeres and undergo telomere shortening. In contrast, dysregulated telomere maintenance is a universal property of cancer cells. Understanding the biology and dynamics of telomeres has far-reaching implications for human health and medicine.