Telomeres are DNA and protein structures that form complexes protecting the ends of chromosomes. Understanding of the mechanisms maintaining telomeres and insights into their function have advanced considerably in recent years. This review summarizes the currently known components of the telomere/telomerase functional complex, and focuses on how they act in the control of processes occurring at telomeres. These include processes acting on the telomeric DNA and on telomeric proteins. Key among them are DNA replication and elongation of one telomeric DNA strand by telomerase. In some situations, homologous recombination of telomeric and subtelomeric DNA is induced. All these processes act to replenish or restore telomeres. Conversely, degradative processes that shorten telomeric DNA, and nonhomologous end-joining of telomeric DNA, can lead to loss of telomere function and genomic instability. Hence they too must normally be tightly controlled.
Telomeres are nucleoprotein structures present at the ends of eukaryotic chromosomes that play a central role in guarding the integrity of the genome by protecting chromosome ends from degradation and fusion. Length regulation is central to telomere function. To broaden our knowledge about the mechanisms that control telomere length, we have carried out a systematic examination of Ϸ4,800 haploid deletion mutants of Saccharomyces cerevisiae for telomere-length alterations. By using this screen, we have identified >150 candidate genes not previously known to affect telomere length. In two-thirds of the identified mutants, short telomeres were observed; whereas in one-third, telomeres were lengthened. The genes identified are very diverse in their functions, but certain categories, including DNA and RNA metabolism, chromatin modification, and vacuolar traffic, are overrepresented. Our results greatly enlarge the number of known genes that affect telomere metabolism and will provide insights into how telomere function is linked to many other cellular processes.
Telomeres, the specialized DNA-protein structures at the ends of eukaryotic chromosomes, are required for chromosomal stability and integrity. 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 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. Here we show that the phenotypic severity of previously described telomerase RNA (ter1) mutations 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.
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