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J. Cell Biol.,
Volume 145, Number 2, April 19, 1999 203-214
Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143-0414
Telomeres are the protein-nucleic acid structures at the ends of eukaryote chromosomes. Tandem
repeats of telomeric DNA are templated by the RNA
component (TER1) of the ribonucleoprotein telomerase. These repeats are bound by telomere binding
proteins, which are thought to interact with other factors to create a higher-order cap complex that stabilizes
the chromosome end. In the budding yeast Kluyveromyces lactis, the incorporation of certain mutant DNA
sequences into telomeres leads to uncapping of telomeres, manifested by dramatic telomere elongation and
increased length heterogeneity (telomere deregulation). Here we show that telomere deregulation leads
to enlarged, misshapen "monster" cells with increased
DNA content and apparent defects in cell division.
However, such deregulated telomeres became stabilized at their elongated lengths upon addition of only a
few functionally wild-type telomeric repeats to their
ends, after which the frequency of monster cells decreased to wild-type levels. These results provide evidence for the importance of the most terminal repeats
at the telomere in maintaining the cap complex essential for normal telomere function. Analysis of uncapped
and capped telomeres also show that it is the deregulation resulting from telomere uncapping, rather than excessive telomere length per se, that is associated with
DNA aberrations and morphological defects.
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