CONTROL OF TELOMERE GROWTH BY INTERACTIONS OF RAP1 WITH THE MOST DISTAL TELOMERIC REPEATS

TELOMERES, the specialized DNA-protein structures at the ends of eukar yotic chromosomes, are required for chromosomal stability and integrit y(1-3). Regulation of the overall length of the telomeric DNA repeat t ract is likely to be a key requirement for its various biological role s. We have studied telomere length regulation in the yeast Kluyveromyc es lactis, which has long (25 base pairs) homogeneous telomeric repeat units(4) that make it highly suitable for telomere studies. In the re lated Saccharomyces cerevisiae, the DNA-sequence-specific duplex-bindi ng protein RAP1 is a component of the telomeric complex(5-9). Here we show that the phenotypic severity of previously described telomerase R NA (ter1) mutations(10) is directly proportional to the loss of RAP1 b inding to mutated telomeric repeats. Using a carboxy-terminal-tail mut ant of K. lactis RAP1, we also show that, unexpectedly, RAP1 interacti on with the most terminal telomeric repeats is crucial for telomere le ngth control.