The telomerase cycle: normal and pathological aspects

Abstract

Telomeres are nucleoprotein complexes that cap the end of eukaryotic chromosomes and are essential for their function and stability. Telomerase, a reverse transcriptase that extends the single-stranded G-rich 3' protruding ends of chromosomes, stabilizes telomere length in germ line cells and regenerative tissues as well as in tumor cells. In the absence of telomerase telomeres shorten with cell division, a process able to trigger cell growth arrest. When telomerase is present in the cell, its activity is tightly regulated at its site of action by factors specifically bound to the telomeric DNA. Recent data indicate that telomeres reorganize during the cell cycle. This review summarizes our current knowledge on how telomeres are dynamically organized and remodeled during cell cycle and stress response, pointing out the conservation and the difference between yeast and human. We then focus on the cellular consequences of telomere modifications in normal and cancer cells. This leads to a discussion of the different roles, seemingly contradictory, of telomeres and telomerase during the initiation and the progression of a cancer.