title: Regulation of telomere length by an N-terminal region of the yeast telomerase reverse transcriptase.
abstract: Telomerase is a reverse transcriptase that maintains chromosome integrity through synthesis of repetitive telomeric sequences on the ends of eukaryotic chromosomes. In the yeast Saccharomyces cerevisiae, telomere length homeostasis is achieved through negative regulation of telomerase access to the chromosome terminus by telomere-bound Rap1 protein and its binding partners, Rif1p and Rif2p, and positive regulation by factors such as Ku70/80, Tel1p, and Cdc13p. Here we report the identification of mutations within an N-terminal region (region I) of the yeast telomerase catalytic subunit (Est2p) that cause telomere lengthening without altering measurable catalytic properties of the enzyme in vitro. These telomerase mutations affect telomere length through a Ku-independent mechanism and do not alter chromosome end structure. While Tel1p is required for expression of the telomere-lengthening phenotype, Rif1p and Rif2p are not, suggesting that telomere overextension is independent of Rap1p. Taken together, these data suggest that specific amino acids within region I of the catalytic subunit of yeast telomerase play a previously unanticipated role in the response to Tel1p regulation at the telomere.
authors.affiliation: Vanderbilt University, Department of Biological Sciences, VU Station B, Nashville, TN 37235, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Platts
authors.forename: Latif M
authors.initials: LM
authors.lastname: Dharamsi
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Friedman
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology* / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C105362:RIF2 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C081647:high affinity DNA-binding factor, S cerevisiae; C074461:RIF1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae; D019098:Telomerase