title: Pol12, the B subunit of DNA polymerase alpha, functions in both telomere capping and length regulation.
abstract: The regulation of telomerase action, and its coordination with conventional DNA replication and chromosome end "capping," are still poorly understood. Here we describe a genetic screen in yeast for mutants with relaxed telomere length regulation, and the identification of Pol12, the B subunit of the DNA polymerase alpha (Pol1)-primase complex, as a new factor involved in this process. Unlike many POL1 and POL12 mutations, which also cause telomere elongation, the pol12-216 mutation described here does not lead to either reduced Pol1 function, increased telomeric single-stranded DNA, or a reduction in telomeric gene silencing. Instead, and again unlike mutations affecting POL1, pol12-216 is lethal in combination with a mutation in the telomere end-binding and capping protein Stn1. Significantly, Pol12 and Stn1 interact in both two-hybrid and biochemical assays, and their synthetic-lethal interaction appears to be caused, at least in part, by a loss of telomere capping. These data reveal a novel function for Pol12 and a new connection between DNA polymerase alpha and Stn1. We propose that Pol12, together with Stn1, plays a key role in linking telomerase action with the completion of lagging strand synthesis, and in a regulatory step required for telomere capping.
authors.affiliation: Department of Molecular Biology and NCCR program "Frontiers in Genetics," University of Geneva, Geneva 4, CH-1211 Switzerland.
authors.forename: Simona
authors.initials: S
authors.lastname: Grossi
authors.forename: Andrea
authors.initials: A
authors.lastname: Puglisi
authors.forename: Petr V
authors.initials: PV
authors.lastname: Dmitriev
authors.forename: Massimo
authors.initials: M
authors.lastname: Lopes
authors.forename: David
authors.initials: D
authors.lastname: Shore
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D004256:DNA Polymerase I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019915:DNA Primase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D009154:Mutation; D010641:Phenotype; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; D034501:Telomere-Binding Proteins; D019915:DNA Primase; C116932:DNA polymerase alpha-primase; D004256:DNA Polymerase I