Dynamics of telomere recombination in the yeast Kluyveromyces lactis
Bechard, Laura Harris
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Telomeres are normally maintained by the enzyme telomerase. While telomerase is active in germline and stem cells in humans, it is inactive in most somatic cells. However, 90% of human cancers have telomerase activity that acts to immortalize cancer cells. A significant minority of cancers use another pathway, called Alternative Lengthening of Telomeres (ALT) to generate long and heterogeneous telomeres by recombination. However, the pathways which lead to ALT cancers are not well understood. Telomerase deletion mutants in the yeasts Saccharomyces cerevisiae and Kluyveromyces lactis have been extensively used as model systems to study recombination at telomeres. In our studies, using telomeric repeats known to be disrupted in Rap1p binding, we have shown that recombinational telomere elongation can occur that more closely resembled that of ALT cancers. This suggests that Rap1p acts to inhibit telomeric recombination. In a second study, we observed the fate of a single abnormally long telomere composed of mutationally tagged “Bcl” repeats in otherwise wild type K. lactis cells. We saw frequent truncations of this telomere to near wild type size. Our data indicate that many of these apparent truncations to wild type size actually shortened the telomere to well below wild type size prior to being re-extended by telomerase. We also demonstrated that the long Bcl telomere could become further elongated by a recombinational process that added additional Bcl repeats onto it. Our results suggest that recombination might be more common at normal telomeres than has been previously recognized.