Control of telomere growth by interactions of RAP1 with the most distal telomeric repeats

TELOMERES, the specialized DNA-protein structures at the ends of eukaryotic chromosomes, are required for chromosomal stability and integrity(1-3). Regulation of the overall length of the telomeric DNA repeat tract is likely to be a key requirement for its various biological roles. We have studied telomere length regulation in the yeast Kluyveromyces lactis, which has long (25 base pairs) homogeneous telomeric repeat units(4) that make it highly suitable for telomere studies. In the related Saccharomyces cerevisiae, the DNA-sequence-specific duplex-binding protein RAP1 is a component of the telomeric complex(5-9). Here we show that the phenotypic severity of previously described telomerase RNA (ter1) mutations(10) is directly proportional to the loss of RAP1 binding to mutated telomeric repeats. Using a carboxy-terminal-tail mutant of K. lactis RAP1, we also show that, unexpectedly, RAP1 interaction with the most terminal telomeric repeats is crucial for telomere length control.