Figure 1.

Effect of alternative strategies for telomere-based targeting of cancer. Telomere structure is schematized consistent with the loop configuration described by Griffith et al. (20). Solid lines represent telomeric DNA and dashed lines represent subtelomeric DNA. The black line represents the 3′ terminus with single-strand overhang. Green and blue ovals are representative of telomere-associated proteins. (A) An immune response is induced against telomerase TERT peptides presented on the surface of TERT-expressing cells, eliminating these cells. The telomere complex and telomerase activity are not directly affected by this therapeutic intervention. (B) Inhibition of telomerase activity results in progressive telomere shortening due to the uncompensated consequences of chromosomal replication. Critical telomere shortening results in loss of telomere function, in turn leading to increased apoptosis and inhibition of cell replication. (C) Expression of mutant telomerase RNA template leads to synthesis of mutant telomere DNA, mutations denoted by *. Mutant telomeric DNA may fail to participate in DNA-protein or DNA-DNA interactions necessary for telomere capping function. The consequences may be similar or identical to those resulting from telomere shortening.