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Gene Review

PIF1  -  Pif1p

Saccharomyces cerevisiae S288c

Synonyms: ATP-dependent DNA helicase PIF1, DNA repair and recombination helicase PIF1, Petite integration frequency protein 1, TST1, Telomere stability protein 1, ...
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High impact information on PIF1

  • The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA [1].
  • Moreover, mutations in PIF1 caused all telomeres to lengthen [2].
  • De novo telomere formation after HO-induced chromosome breakage also occurred at elevated frequencies in pif1 cells [2].
  • The loss of expression of subtelomeric genes in pif1 cells was due to deletion of the subtelomeric regions of the chromosomes and the generation of new telomeres at proximal sites [2].
  • As the two Pif1p subfamily members studied to date affect the same DNA sequences, the amino acid similarity that defines this subfamily might reflect common substrates [3].

Biological context of PIF1

  • Null mutations in ABF2 or PIF1, two genes implicated in mtDNA maintenance and recombination, exhibit a synthetic-petite phenotype in combination with ntg1 null mutations that is accompanied by enhanced mtDNA point mutagenesis in the corresponding double-mutant strains [4].
  • Both defects result in increased genome instability that is normally suppressed by these checkpoints, RAD52-dependent recombination, and PIF1-dependent inhibition of de novo telomere addition [5].
  • The potential human homolog of the yeast PIF1 gene has been cloned from the cDNA library of the Hek293 cell line [6].
  • A suppressor of this thermosensitive phenotype was isolated from a wild-type plasmid library by transforming a pif1 null strain to growth on glycerol at the non-permissive temperature [7].
  • Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta [8].

Anatomical context of PIF1


Associations of PIF1 with chemical compounds

  • The overproduced PIF1 protein, which is firmly associated with insoluble mitochondrial structures, has been partially purified in a mitochondrial nuclease deficient nuc1 strain by a procedure including solubilization by urea and renaturation by dialysis at alkaline pH [9].
  • Deletion of PIF1 also suppresses the cold-sensitive lethality and hydroxyurea sensitivity of the pol32delta strain [8].
  • Elimination of Ntg1p and Pif1p resulted in a synergistic corruption of respiratory competency upon exposure to antimycin and H(2)O(2) [10].
  • We show that pif1 mutant cells are sensitive to ethidium bromide-induced damage and this mtDNA is prone to fragmentation [11].

Physical interactions of PIF1

  • In vivo, overexpression of Pif1p reduces telomerase association with telomeres, whereas depleting cells of Pif1p increases the levels of telomere-bound Est1p, a telomerase subunit that is present on the telomere when telomerase is active [12].

Regulatory relationships of PIF1

  • Specifically, we show that deletion of PIF1 suppresses the lethality of a DNA2-null mutant [8].
  • In the presence of the up-mutations, however, the ability of the Pif1p helicase to decrease telomere length and to inhibit the association of Est1p with telomeres is impaired [13].

Other interactions of PIF1

  • Thus, suppression of dna2delta can be rationalized if deletion of POL32 and/or PIF1 results in a reduction in long flaps that require Dna2 for processing [8].
  • In addition, deletion of RRM3 or SML1 fully rescued the approximately 50% depletion of mtDNA observed in a pif1 null strain [14].
  • The PIF1 and MRS2 gene products have previously been shown to be essential for mitochondrial DNA maintenance at elevated temperatures and mitochondrial group II intron splicing, respectively, in the yeast Saccharomyces cerevisiae [15].
  • PIF1: a DNA helicase in yeast mitochondria [9].
  • We propose that, in addition to its catalytic role, the finger subdomain of Est2p facilitates the action of Pif1p at telomeres [13].


  1. The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA. Ivessa, A.S., Zhou, J.Q., Zakian, V.A. Cell (2000) [Pubmed]
  2. The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation. Schulz, V.P., Zakian, V.A. Cell (1994) [Pubmed]
  3. The Pif1p subfamily of helicases: region-specific DNA helicases? Bessler, J.B., Torredagger, J.Z., Zakian, V.A. Trends Cell Biol. (2001) [Pubmed]
  4. Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteins. O'Rourke, T.W., Doudican, N.A., Mackereth, M.D., Doetsch, P.W., Shadel, G.S. Mol. Cell. Biol. (2002) [Pubmed]
  5. Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability. Myung, K., Pennaneach, V., Kats, E.S., Kolodner, R.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Characterization of ATPase activity of recombinant human pif1. Huang, Y., Zhang, D.H., Zhou, J.Q. Acta Biochim. Biophys. Sin. (Shanghai) (2006) [Pubmed]
  7. A single-stranded DNA binding protein required for mitochondrial DNA replication in S. cerevisiae is homologous to E. coli SSB. Van Dyck, E., Foury, F., Stillman, B., Brill, S.J. EMBO J. (1992) [Pubmed]
  8. Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta. Budd, M.E., Reis, C.C., Smith, S., Myung, K., Campbell, J.L. Mol. Cell. Biol. (2006) [Pubmed]
  9. PIF1: a DNA helicase in yeast mitochondria. Lahaye, A., Stahl, H., Thines-Sempoux, D., Foury, F. EMBO J. (1991) [Pubmed]
  10. Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae. Doudican, N.A., Song, B., Shadel, G.S., Doetsch, P.W. Mol. Cell. Biol. (2005) [Pubmed]
  11. The role of Pif1p, a DNA helicase in Saccharomyces cerevisiae, in maintaining mitochondrial DNA. Cheng, X., Dunaway, S., Ivessa, A.S. Mitochondrion (2007) [Pubmed]
  12. The yeast Pif1p helicase removes telomerase from telomeric DNA. Boulé, J.B., Vega, L.R., Zakian, V.A. Nature (2005) [Pubmed]
  13. The finger subdomain of yeast telomerase cooperates with Pif1p to limit telomere elongation. Eugster, A., Lanzuolo, C., Bonneton, M., Luciano, P., Pollice, A., Pulitzer, J.F., Stegberg, E., Berthiau, A.S., Förstemann, K., Corda, Y., Lingner, J., Géli, V., Gilson, E. Nat. Struct. Mol. Biol. (2006) [Pubmed]
  14. The conserved Mec1/Rad53 nuclear checkpoint pathway regulates mitochondrial DNA copy number in Saccharomyces cerevisiae. Taylor, S.D., Zhang, H., Eaton, J.S., Rodeheffer, M.S., Lebedeva, M.A., O'rourke, T.W., Siede, W., Shadel, G.S. Mol. Biol. Cell (2005) [Pubmed]
  15. Overexpression of a novel member of the mitochondrial carrier family rescues defects in both DNA and RNA metabolism in yeast mitochondria. Van Dyck, E., Jank, B., Ragnini, A., Schweyen, R.J., Duyckaerts, C., Sluse, F., Foury, F. Mol. Gen. Genet. (1995) [Pubmed]
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