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dc.contributor.authorFerguson, JL
dc.contributor.authorChao, WCH
dc.contributor.authorLee, E
dc.contributor.authorFriedman, KL
dc.identifier.citationPLOS ONE, 2013, 8
dc.description.abstractTelomerase is a multi-subunit enzyme that reverse transcribes telomere repeats onto the ends of linear eukaryotic chromosomes and is therefore critical for genome stability. S. cerevisiae telomerase activity is cell-cycle regulated; telomeres are not elongated during G1 phase. Previous work has shown that Est1 protein levels are low during G1 phase, preventing telomerase complex assembly. However, the pathway targeting Est1p for degradation remained uncharacterized. Here, we show that Est1p stability through the cell cycle mirrors that of Clb2p, a known target of the Anaphase Promoting Complex (APC). Indeed, Est1p is stabilized by mutations in both essential and non-essential components of the APC. Mutations of putative Destruction boxes (D-boxes), regions shown to be important for recognition of known APC substrates, stabilize Est1p, suggesting that Est1p is likely to be targeted for degradation directly by the APC. However, we do not detect degradation or ubiquitination of recombinant Est1p by the APC in vitro, suggesting either that the recombinant protein lacks necessary post-translational modification and/or conformation, or that the APC affects Est1p degradation by an indirect mechanism. Together, these studies shed light on the regulation of yeast telomerase assembly and demonstrate a new connection between telomere maintenance and cell cycle regulation pathways.
dc.titleThe Anaphase Promoting Complex Contributes to the Degradation of the S. cerevisiae Telomerase Recruitment Subunit Est1p
dc.typeJournal Article
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPLOS ONE
pubs.notesaffiliation: Friedman, KL (Reprint Author), Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA. Ferguson, Jenifer L.; Friedman, Katherine L., Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA. Chao, William Chong Hang, Inst Canc Res, Sect Struct Biol, London SW3 6JB, England. Lee, Ethan, Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN USA. article-number: e55055 keywords-plus: YEAST SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; BUDDING YEAST; DEPENDENT DEGRADATION; DESTRUCTION BOX; MITOTIC EXIT; REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT; PHOSPHATASE CDC14; G1 CYCLINS research-areas: Science & Technology - Other Topics web-of-science-categories: Multidisciplinary Sciences author-email: [email protected] funding-acknowledgement: Vanderbilt University; National Institutes of Health (NIH) [GM080393]; ICR; Vanderbilt Ingram Cancer Center [P30 CA68485]; Vanderbilt Digestive Disease Research Center [DK058404] funding-text: This project was supported by Vanderbilt University and a National Institutes of Health (NIH) grant GM080393 to KLF. WCHC was funded by an ICR studentship. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource and supported by the Vanderbilt Ingram Cancer Center (P30 CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. number-of-cited-references: 86 times-cited: 7 usage-count-last-180-days: 0 usage-count-since-2013: 3 journal-iso: PLoS One doc-delivery-number: 093RV unique-id: ISI:000315210400053 oa: gold da: 2018-08-06
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dc.contributor.icrauthorChao, William Chong Hangen

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