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dc.contributor.advisor Counter, Christopher M en_US
dc.contributor.author Barrientos, KS
dc.contributor.author Kendellen, MF
dc.contributor.author Freibaum, BD
dc.contributor.author Armbruster, BN
dc.contributor.author Etheridge, KT
dc.contributor.author Counter, CM
dc.coverage.spatial United States
dc.date.accessioned 2009-08-27T18:39:42Z
dc.date.issued 2008-09
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/18519588
dc.identifier MCB.00048-08
dc.identifier.citation Mol Cell Biol, 2008, 28 (17), pp. 5251 - 5264
dc.identifier.uri http://hdl.handle.net/10161/1343
dc.description Dissertation en_US
dc.description.abstract The mammalian protein POT1 binds to telomeric single-stranded DNA (ssDNA), protecting chromosome ends from being detected as sites of DNA damage. POT1 is composed of an N-terminal ssDNA-binding domain and a C-terminal protein interaction domain. With regard to the latter, POT1 heterodimerizes with the protein TPP1 to foster binding to telomeric ssDNA in vitro and binds the telomeric double-stranded-DNA-binding protein TRF2. We sought to determine which of these functions-ssDNA, TPP1, or TRF2 binding-was required to protect chromosome ends from being detected as DNA damage. Using separation-of-function POT1 mutants deficient in one of these three activities, we found that binding to TRF2 is dispensable for protecting telomeres but fosters robust loading of POT1 onto telomeric chromatin. Furthermore, we found that the telomeric ssDNA-binding activity and binding to TPP1 are required in cis for POT1 to protect telomeres. Mechanistically, binding of POT1 to telomeric ssDNA and association with TPP1 inhibit the localization of RPA, which can function as a DNA damage sensor, to telomeres.
dc.format.extent 5251 - 5264
dc.format.mimetype application/pdf
dc.language eng
dc.language.iso en_US
dc.relation.ispartof Mol Cell Biol
dc.relation.isversionof 10.1128/MCB.00048-08
dc.subject Cell Line
dc.subject DNA Damage
dc.subject DNA, Single-Stranded
dc.subject Humans
dc.subject Models, Biological
dc.subject Mutant Proteins
dc.subject Mutation
dc.subject Protein Binding
dc.subject Protein Transport
dc.subject Replication Protein A
dc.subject Telomere
dc.subject Telomere-Binding Proteins
dc.subject Telomeric Repeat Binding Protein 2
dc.title Distinct functions of POT1 at telomeres.
dc.type Journal Article
dc.department Pharmacology en_US
duke.embargo.months 24 en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/18519588
pubs.issue 17
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Pharmacology & Cancer Biology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Radiation Oncology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published
pubs.volume 28
dc.identifier.eissn 1098-5549

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