TELOMERE FUNCTIONS - LESSONS FROM YEAST

Telomeres are specialized DNA-protein structures that form tile ends o f eukaryotic chromosomes. In yeast, loss of even a single telomere cau ses a prolonged, but transitory, cell-cycle arrest. During this arrest , many broken chromosomes acquire a new telomere by one of three pathw ays, although at the cost of a partial loss of heterozygosity. In addi tion, a substantial fraction of the chromosomes lacking a telomere is lost, which generates art aneuploid cell. In these cases, the broken c hromosome is usually replicated and segregated for ten or more cell di visions in unstable form. Extrapolation from yeast suggests that the g radual loss of telomeric DNA that accompanies ageing in humans may ini tiate the kinds of chromosomal rearrangements and genetic changes that are associated with tumorigenesis.