Nature 383, 354 - 357 (26 September 1996); doi:10.1038/383354a0

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

Anat Krauskopf & Elizabeth H. Blackburn

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California 94143-0414, USA

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 units⁴ 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 (terl) mutations¹⁰ 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.

References

1.	Greider, C. W. Annu. Rev. Biochem. 65, 337−365 (1996). | Article | PubMed | ISI | ChemPort |
2.	Blackburn, E. H. Cell 77, 621−623 (1994). | Article | PubMed | ISI | ChemPort |
3.	Zakian, V. A. Science 270, 1601−1607 (1995). | PubMed | ISI | ChemPort |
4.	McEachem, M. J. & Blackburn, E. H. Proc. Natl Acad. Sci. USA 91, 3453−3457 (1994). | PubMed | ChemPort |
5.	Berman, J., Tachibana, C. Y. & Tye, B.-K. Proc. Natl Acad. Sci. USA 83, 3713−3717 (1986). | PubMed | ChemPort |
6.	Buchman, A. R., Lue, N. F. & Kornberg, R. D. Mol. Cell. Biol. 8, 5086−5099 (1988). | PubMed | ISI | ChemPort |
7.	Conrad, M. N., Wright, J. H., Wolf, A. J. & Zakian, V. A. Cell 63, 739−750 (1990). | Article | PubMed | ISI | ChemPort |
8.	Shore, D. & Nasmyth, K. Cell 51, 721−732 (1989).
9.	Shore, D. Trends Genet. 10, 408−412 (1994). | Article | PubMed | ISI | ChemPort |
10.	McEachern, M. J. & Blackburn, E. H. Nature 376, 403−409 (1995). | Article | PubMed | ISI | ChemPort |
11.	Liu, C., Mao, X. & Lustig, A. Genetics 138, 1025−1040 (1994). | PubMed | ISI | ChemPort |
12.	Larson, G. P., Castanotto, D., Rossi, J. J. & Malafa, M. P. Gene 150, 35−41 (1994). | Article | PubMed | ISI | ChemPort |
13.	Gilson, E., Roberge, M., Giraldo, R., Rhodes, D. & Gasser, S. J. Mol. Biol. 231, 293−310 (1993). | Article | PubMed | ISI | ChemPort |
14.	Palladino, F. et al. Cell 75, 543−556 (1993). | Article | PubMed | ISI | ChemPort |
15.	Fang, G. & Cech, T. R. in Telomeres (eds Greider, C. W. & Blackburn, E. H.) 69−105 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1995). | ChemPort |
16.	Buck, S. W. & Shore, D. Genes Dev. 9, 370−384 (1995). | PubMed | ISI | ChemPort |
17.	Moretti, P., Freeman, K., Coodly, L. & Shore, D. Genes Dev. 8, 2257−2269 (1994). | PubMed | ISI | ChemPort |
18.	Chen, X.-J. & Clark-Walker, G. D. Mol. Cell Biol. 14, 4501−4508 (1994). | PubMed | ISI | ChemPort |
19.	Kurtz, S. & Shore, D. Genes Dev. 5, 616−628 (1991). | PubMed | ISI | ChemPort |