Telomeres: what’s new at your end?

The ends of linear eukaryotic chromosomes, the telomeres, fulfill unique and essential functions in genome integrity. First and above all, they represent the ends of the DNA molecules. In general, non-telomeric double-strand DNA breaks (DSBs) are not tolerated and are rapidly repaired. This scenario, however, does not apply to telomeres (Muller, 1938; McClintock, 1939). Indeed, telomeric chromosome ends are bound by a complex cast of factors that protect chromosome ends from degradation or fusion (d’Adda di Fagagna et al., 2004). Second, owing to the semi-conservative synthesis of DNA, a DNA end cannot be completely duplicated (Watson, 1972; Olovnikov, 1973). To avoid continuous sequence loss from the telomeres in dividing cells, special mechanisms have evolved. In most eukaryotic organisms, the solution to the problem involves a ribonuclear complex, called telomerase, that is minimally composed of a reverse transcriptase catalytic protein subunit and an RNA subunit that is used as the template (Greider and Blackburn, 1987). In order to accommodate these two functions, the overall telomere structure is dynamic and undergoes dramatic changes during the cell cycle particularly in S phase (Blackburn, 2001; Vega et al., 2003; Smogorzewska and de Lange, 2004). Telomere structure and function have been most intensely studied in model systems such as budding yeast and in human cell lines. Therefore, we chose these organisms to illustrate similarities and differences in telomere composition and structure. Telomeric DNA structures are highly conserved amongst eukaryotes. In virtually all organisms, chromosomes end with an array of short direct repeats. For example, human telomeres comprise 2-20 kb of (TTAGGG)n repeats. The species-specific repeats are related to each other, each being composed of a G-rich and a C-rich strand. Moreover, the directionality of the repeats is conserve