Introduction

Telomeres are DNA/protein structures at the ends of chromosomes, needed to protect chromosome ends from degradation and distinguish them from double-stranded breaks (de Lange 2002). Human telomere DNA consists of thousands of repeats of TTAGGG.

DNA polymerase I cannot copy the extreme end of a DNA strand (Watson 1972), so telomeres would tend to get shorter with each cell division. In germ cells (Wright et al. 1996), some stem cells (Chiu et al. 1996, Harle-Bachor and Boukamp 1996) and most cancer cells (Kim et al. 1994, Broccoli et al. 1995), telomeres are maintained by the action of the enzyme telomerase (Greider and Blackburn 1985), which contains two core components, a reverse transcriptase TERT (telomerase reverse transcriptase), and an RNA molecule, TERC (telomerase RNA component), that acts as a template for the synthesis of the telomere repeats. Telomerase is active in HSCs, but there is shortening of telomeres during ageing (Vaziri et al. 1994), indicating that the level of telomerase activity is not sufficient to stabilize telomeres in ageing stem cells (see also Zimmermann and Martens, this volume).

In the absence of telomerase in most somatic cells, telomeres do shorten with each cell division (Harley et al. 1990). In most tissues, therefore, telomere length decreases with age (Vaziri et al. 1994), reflecting the history of cell division.

0 0

Post a comment