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dc.contributor.advisor Counter, Christopher M en_US
dc.contributor.author Freibaum, Brian David en_US
dc.date.accessioned 2008-08-01T12:53:15Z
dc.date.available 2011-07-26T04:30:03Z
dc.date.issued 2008-04-10 en_US
dc.identifier.uri http://hdl.handle.net/10161/651
dc.description Dissertation en_US
dc.description.abstract <p>Telomeres are the ends of chromosomes which are composed of repetitive DNA sequence and telomere associated proteins. In C. elegans, the protein F39H2.5 was found to associate with the telomere, regulating both telomere length and genomic integrity. F39H2.5 is a member of the β-CASP family of proteins that are known to possess nuclease activity on DNA substrates. I thus sought to address whether any of the human β-CASP family proteins associated with telomeres. Here I show that hSnm1B localized to the telomere indirectly, via interaction with the double-stranded telomere binding protein TRF2. The terminal 37 amino acids of hSnm1B are necessary and sufficient for binding TRF2, and moreover that binding to TRF2 stabilized hSnm1B protein by preventing ubiquitination. In the absence of exogenous TRF2 this domain acted as a degron, promoting protein instability. I thus termed the domain the Protection And INstability (PAIN) domain. I hypothesize that TRF2 binding ensures that hSnm1B will only accumulate at telomeres by preventing the degradation of hSnm1B. However, hSnm1B stability appears to be further regulated, as telomere specific DNA damage stabilized hSnm1B independent of the PAIN domain. Thus, it appears that the telomere associated protein, hSnm1B, is regulated by protein stability in a manner that is both dependent and independent of the PAIN domain.</p> en_US
dc.format.extent 16402583 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Biology, Molecular en_US
dc.subject Biology, Cell en_US
dc.subject Biology, Genetics en_US
dc.subject hSnm en_US
dc.subject B en_US
dc.subject TRF en_US
dc.subject telomere en_US
dc.title Characterization of the Novel Telomere Associated Protein: hSnm1B en_US
dc.type Dissertation en_US
dc.department Pharmacology en_US
duke.embargo.months 24 en_US

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