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dc.contributor.authorBechard, Laura Harris
dc.date.accessioned2014-03-04T18:26:25Z
dc.date.available2014-03-04T18:26:25Z
dc.date.issued2010-05
dc.identifier.otherbechard_laura_h_201005_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/bechard_laura_h_201005_phd
dc.identifier.urihttp://hdl.handle.net/10724/26232
dc.description.abstractTelomeres 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.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjecttelomere
dc.subjectrecombination
dc.subjectKluyveromyces lactis
dc.subjectAlternative Lengthening of Telomeres
dc.subjectsurvivor
dc.subjectRap1
dc.subjectTelomere Rapid Deletion
dc.titleDynamics of telomere recombination in the yeast Kluyveromyces lactis
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentGenetics
dc.description.majorGenetics
dc.description.advisorMichael McEachern
dc.description.committeeMichael McEachern
dc.description.committeeMichael Terns
dc.description.committeeWalter Schmidt
dc.description.committeeMichelle Momany
dc.description.committeeSidney Kushner


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