title: Replication proteins influence the maintenance of telomere length and telomerase protein stability.
abstract: We investigated the effects of fission yeast replication genes on telomere length maintenance and identified 20 mutant alleles that confer lengthening or shortening of telomeres. The telomere elongation was telomerase dependent in the replication mutants analyzed. Furthermore, the telomerase catalytic subunit, Trt1, and the principal initiation and lagging-strand synthesis DNA polymerase, Polalpha, were reciprocally coimmunoprecipitated, indicating these proteins physically coexist as a complex in vivo. In a polalpha mutant that exhibited abnormal telomere lengthening and slightly reduced telomere position effect, the cellular level of the Trt1 protein was significantly lower and the coimmunoprecipitation of Trt1 and Polalpha was severely compromised compared to those in the wild-type polalpha cells. Interestingly, ectopic expression of wild-type polalpha in this polalpha mutant restored the cellular Trt1 protein to the wild-type level and shortened the telomeres to near-wild-type length. These results suggest that there is a close physical relationship between the replication and telomerase complexes. Thus, mutation of a component of the replication complex can affect the telomeric complex in maintaining both telomere length equilibrium and telomerase protein stability.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Dahlén
authors.forename: Per
authors.initials: P
authors.lastname: Sunnerhagen
authors.forename: Teresa S-F
authors.initials: TS
authors.lastname: Wang
mesh_terms: D020134:Catalytic Domain; D004256:DNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D019915:DNA Primase / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins; D004795:Enzyme Stability; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D016259:Genes, myc; D046911:Macromolecular Substances; D009154:Mutation; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D029702:Schizosaccharomyces pombe Proteins; C509188:trt1 protein, S pombe; D019915:DNA Primase; D019098:Telomerase; D004256:DNA Polymerase I