Influence of nucleoside analogue treatment on telomere length and TRF2 amount in human HL60 cells.

Long-term treatment with 3'-azido-2',3'-dideoxy-guanosine (AZddG) results in reproducible telomere shortening in cultured human HL60 cells. TRF2 protein has been implicated in the protection of chromosome ends. It binds to double-strand repeats and may have an indirect role in protecting the G-rich overhang by recruiting other telomere-binding proteins to the G-tail or by mediating the formation of the telomeric t-loop. Western blot analysis demonstrated no change or a slight increase, of the TRF2 protein level in HL60 cells with AZddG-induced telomere shortening. The effects of nucleoside analogues on TRF2 suggest that it is not telomere length per se, but rather the presence or absence of a protective telomere state, which determines whether senescence ensues.