title: The Pif1 family helicase Pfh1 facilitates telomere replication and has an RPA-dependent role during telomere lengthening.
abstract: Pif1 family helicases are evolutionary conserved 5'-3' DNA helicases. Pfh1, the sole Schizosaccharomyces pombe Pif1 family DNA helicase, is essential for maintenance of both nuclear and mitochondrial DNAs. Here we show that its nuclear functions include roles in telomere replication and telomerase action. Pfh1 promoted semi-conservative replication through telomeric DNA, as replication forks moved more slowly through telomeres when Pfh1 levels were reduced. Unlike other organisms, S. pombe cells overexpressing Pfh1 displayed markedly longer telomeres. Because this lengthening occurred in the absence of homologous recombination but not in a replication protein A mutant (rad11-D223Y) that has defects in telomerase function, it is probably telomerase-mediated. The effects of Pfh1 on telomere replication and telomere length are likely direct as Pfh1 exhibited high telomere binding in cells expressing endogenous levels of Pfh1. These findings argue that Pfh1 is a positive regulator of telomere length and telomere replication.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
authors.forename: Karin R
authors.initials: KR
authors.lastname: McDonald
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Nasim
authors.initials: N
authors.lastname: Sabouri
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Webb
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA. Electronic address: vzakian@princeton.edu.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Zakian
mesh_terms: D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D051716:Replication Protein A / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000502:physiology*
chemical_list: C480031:Rad11 protein, S pombe; D051716:Replication Protein A; D029702:Schizosaccharomyces pombe Proteins; D004265:DNA Helicases; C468287:Pfh1 protein, S pombe
keywords: DNA replication; Pfh1; Pif1 family helicase; Schizosaccharomyces pombe; Telomere