Ciliate telomeres

In their 1985 Cell paper, Greider and Blackburn announced the discovery of an enzyme that extended the DNA at chromosome telomeres in the ciliate, Tetrahymena. Since then, there has been an explosion of knowledge about both the RNA and protein subunits of this unusual ribonucleo-protein enzyme in organisms ranging from the ciliates to yeast to humans. The regulation of telomerase is now understood to take place both at the level of synthesis of the enzyme and via the state of its substrate, the telomere itself The roles of telomerase in both cellular immortality and cancer are vibrant areas of current research. 

Figure 5 Interactions of end-binding proteins with telomeric G-rich overhangs. (A) Human POTl binding disrupts G-quadruplexes to allow extension by telomer-ase at the 3 end of a telomeric overhang. (B) The ciliate end-binding complex TEBPajfi promotes G-quadruplex formation to prevent telomere extension...

Why was G4 DNA not apparent in the cocrystals of telomeric DNA with ciliate TEBP complexes An explanation for this apparent paradox was provided by mutational analysis of TEBP (3, which showed that the basic C-terminal region of TEBPp is necessary to promote G4 DNA formation. Following the common divide and conquer strategy for structural analysis, this region had been truncated in the TEBPa/(3 heterodimer analyzed in the cocrystals. ... 

Comment. There is an eclat difference between telomere replacement in unicellular eukaryotes (like the ciliates) and somatic cells of multicellular hosts (like the mammals). The ciliates immediately cap with telomeres their chromosome ends after each cell division, whereas the chromosome ends of somatic cells in multicellular hosts remain uncapped, and steadily shorten with each cell division (approx 50 bp per cell divisions). These somatic cells of multicellular hosts undergo senescence and die, at which time stem cells may (or may not) replace them. The tetrahymena cells are rejuvenated and escape senescence due to constant telomere repairs. In that, unicellular eukaryotes (example the ciliates) resemble malignantly transformed somatic cells of the multicellular hosts, except that telomerase action is constitutive (irreversible) in the latter, whereas it can accelerate (at conjugation) and decelerate (after conjugation) in the former. 

Prescott JD, DuBois ML, Prescott DM. Evolution of the scrambled germline gene encoding alpha-telomere binding protein in three hypertrichous ciliates. Chromosoma. 

---