The Pif1 family helicase Pfh1 facilitates telomere replication and has an RPA-dependent role during telomere lengthening |
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| Institution: | 1. Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA;2. Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden;1. School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, GR-15771 Athens, Greece;2. Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy;3. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70125 Bari, Italy;3. From the Departments of Molecular Genetics and The Ohio State University, Columbus, Ohio 43210;5. Human Nutrition and The Ohio State University, Columbus, Ohio 43210;4. Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210;6. the Department of Oncological Sciences and University of Utah School of Medicine, Salt Lake City, Utah 84132;12. the Microarray Core Facility and University of Utah School of Medicine, Salt Lake City, Utah 84112;8. Bioinformatics Shared Resource, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112 |
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| 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. |
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| Keywords: | DNA replication Pif1 family helicase Pfh1 Telomere |
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