Home LiteratureArticle Details
PMID: 16935874 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Roles of Pif1-like helicases in the maintenance of genomic stability.

Nucleic acids research ·Vol. 34 ·No. 15 ·2006-00-00 ·Pages 4147-53

Boulé JB, Zakian VA

Abstract

The Pif1p family of DNA helicases is conserved from yeast to humans. To date, four members of this family have been analyzed in some detail by in vitro and in vivo assays: the two baker's yeast helicases, ScPif1p and Rrm3p, the fission yeast Pfh1p and the human enzyme hPif1p. In vitro, these enzymes are 5' to 3' DNA helicase and show little processivity. In vivo, ScPif1p, Rrm3p and probably Pfh1p, function in both the nucleus at specific genomic loci and in mitochondria, where they are needed for the stable maintenance of the genome as accessory helicases to the replication machinery. Interestingly, they act on common DNA substrates but appear to have largely non-overlapping cellular functions, ranging from Okazaki fragment processing, telomerase inhibition, to helping the replication fork progress through non-nucleosomal protein-DNA complexes. For example, both ScPif1p and Rrm3p affect the replication of telomeres, but in a different way: Pif1p inhibits telomerase-mediated telomere elongation by directly removing telomerase from a DNA end, whereas Rrm3p facilitates replication through telomeric DNA. Here we review the current knowledge on the Pif1-like helicases, as a first step towards understanding the basis of their functional specialization and mechanism of action.

MeSH Terms
Conserved Sequence DNA Helicases/chemistry,physiology DNA Replication/physiology Evolution, Molecular Genomic Instability/physiology Humans Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/chemistry
Chemicals
Saccharomyces cerevisiae Proteins PIF1 protein, S cerevisiae DNA Helicases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Boulé Jean-Baptiste
Department of Molecular Biology, Lewis Thomas Laboratories, Princeton University, Princeton, NJ 08544, USA. [email protected]
Zakian Virginia A
References (50)
50 references, click to expand
  1. PIF1 DNA helicase from Saccharomyces cerevisiae. Biochemical characterization of the enzyme.
    J Biol Chem. 1993 Dec 15;268(35):26155-61 PMID: 8253734
  2. RecBCD enzyme is a bipolar DNA helicase.
    Nature. 2003 Jun 19;423(6942):893-7 PMID: 12815438
  3. A gene with specific and global effects on recombination of sequences from tandemly repeated genes in Saccharomyces cerevisiae.
    Genetics. 1993 Nov;135(3):711-8 PMID: 8293975
  4. Repair of chromosome ends after telomere loss in Saccharomyces.
    Mol Biol Cell. 2001 Dec;12(12):4078-89 PMID: 11739802
  5. Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae.
    Nature. 2001 Jun 28;411(6841):1073-6 PMID: 11429610
  6. The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation.
    Cell. 1994 Jan 14;76(1):145-55 PMID: 8287473
  7. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes.
    Nucleic Acids Res. 1989 Jun 26;17(12):4713-30 PMID: 2546125
  8. RecBCD enzyme is a DNA helicase with fast and slow motors of opposite polarity.
    Nature. 2003 Jun 19;423(6942):889-93 PMID: 12815437
  9. Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteins.
    Mol Cell Biol. 2002 Jun;22(12):4086-93 PMID: 12024022
  10. Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae.
    Mol Cell Biol. 2005 Jun;25(12):5196-204 PMID: 15923634
  11. Cell division cycle mutants altered in DNA replication and mitosis in the fission yeast Schizosaccharomyces pombe.
    Mol Gen Genet. 1981;182(1):119-24 PMID: 6943408
  12. The yeast Pif1p helicase removes telomerase from telomeric DNA.
    Nature. 2005 Nov 3;438(7064):57-61 PMID: 16121131
  13. Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdc13 and Est1.
    Mol Cell. 2004 Oct 8;16(1):139-46 PMID: 15469829
  14. The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity.
    Nucleic Acids Res. 2006;34(5):1393-404 PMID: 16522649
  15. Understanding the roles of RecQ helicases in the maintenance of genome integrity and suppression of tumorigenesis.
    Biochem Soc Trans. 2004 Dec;32(Pt 6):957-8 PMID: 15506934
  16. Genetic and biochemical analyses of Pfh1 DNA helicase function in fission yeast.
    Nucleic Acids Res. 2004;32(14):4205-16 PMID: 15302919
  17. DNA helicase Srs2 disrupts the Rad51 presynaptic filament.
    Nature. 2003 May 15;423(6937):305-9 PMID: 12748644
  18. The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes.
    Mol Cell. 2003 Dec;12(6):1525-36 PMID: 14690605
  19. Homologous recombination near and far from DNA breaks: alternative roles and contrasting views.
    Annu Rev Genet. 2001;35:243-74 PMID: 11700284
  20. The puzzle of PCNA's many partners.
    Bioessays. 2000 Nov;22(11):997-1006 PMID: 11056476
  21. Est1p as a cell cycle-regulated activator of telomere-bound telomerase.
    Science. 2002 Aug 9;297(5583):1023-6 PMID: 12169735
  22. PRP16, a DEAH-box RNA helicase, is recruited to the spliceosome primarily via its nonconserved N-terminal domain.
    RNA. 1998 Oct;4(10):1216-29 PMID: 9769096
  23. Telomerase: what are the Est proteins doing?
    Curr Opin Cell Biol. 2003 Jun;15(3):275-80 PMID: 12787768
  24. The amino terminus of the Saccharomyces cerevisiae DNA helicase Rrm3p modulates protein function altering replication and checkpoint activity.
    Genetics. 2004 Nov;168(3):1205-18 PMID: 15579680
  25. Schizosaccharomyces pombe pfh1+ encodes an essential 5' to 3' DNA helicase that is a member of the PIF1 subfamily of DNA helicases.
    Mol Biol Cell. 2002 Jun;13(6):2180-91 PMID: 12058079
  26. Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities.
    Mol Cell Biol. 2004 Apr;24(8):3198-212 PMID: 15060144
  27. Protein displacement by an assembly of helicase molecules aligned along single-stranded DNA.
    Nat Struct Mol Biol. 2004 Jun;11(6):531-8 PMID: 15146172
  28. Fission yeast cdc24 is a replication factor C- and proliferating cell nuclear antigen-interacting factor essential for S-phase completion.
    Mol Cell Biol. 1999 Feb;19(2):1038-48 PMID: 9891039
  29. Integrative analysis of the mitochondrial proteome in yeast.
    PLoS Biol. 2004 Jun;2(6):e160 PMID: 15208715
  30. Pif1p helicase, a catalytic inhibitor of telomerase in yeast.
    Science. 2000 Aug 4;289(5480):771-4 PMID: 10926538
  31. Loss of a yeast telomere: arrest, recovery, and chromosome loss.
    Cell. 1993 Nov 19;75(4):729-39 PMID: 8242745
  32. Saccharomyces cerevisiae RRM3, a 5' to 3' DNA helicase, physically interacts with proliferating cell nuclear antigen.
    J Biol Chem. 2002 Nov 22;277(47):45331-7 PMID: 12239216
  33. Requirement of Rrm3 helicase for repair of spontaneous DNA lesions in cells lacking Srs2 or Sgs1 helicase.
    Mol Cell Biol. 2004 Apr;24(8):3213-26 PMID: 15060145
  34. Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p.
    Genes Dev. 2004 Mar 1;18(5):498-503 PMID: 15037547
  35. Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA.
    Genes Dev. 2002 Jun 1;16(11):1383-96 PMID: 12050116
  36. pif mutation blocks recombination between mitochondrial rho+ and rho- genomes having tandemly arrayed repeat units in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1983 Sep;80(17):5345-9 PMID: 6310571
  37. Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta.
    Mol Cell Biol. 2006 Apr;26(7):2490-500 PMID: 16537895
  38. The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments.
    Nature. 2003 May 15;423(6937):309-12 PMID: 12748645
  39. Telomere replication: an Est fest.
    Curr Biol. 2003 May 27;13(11):R439-41 PMID: 12781153
  40. Hexameric RSF1010 helicase RepA: the structural and functional importance of single amino acid residues.
    Nucleic Acids Res. 2003 Oct 15;31(20):5917-29 PMID: 14530440
  41. The fission yeast pfh1(+) gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase.
    Nucleic Acids Res. 2002 Nov 1;30(21):4728-39 PMID: 12409464
  42. A PIF-dependent recombinogenic signal in the mitochondrial DNA of yeast.
    EMBO J. 1985 Dec 16;4(13A):3525-30 PMID: 16453651
  43. The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA.
    Cell. 2000 Feb 18;100(4):479-89 PMID: 10693764
  44. DNA polymerases that propagate the eukaryotic DNA replication fork.
    Crit Rev Biochem Mol Biol. 2005 Mar-Apr;40(2):115-28 PMID: 15814431
  45. The Pif1p subfamily of helicases: region-specific DNA helicases?
    Trends Cell Biol. 2001 Feb;11(2):60-5 PMID: 11166213
  46. Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability.
    Gene. 2005 Jul 18;354:86-92 PMID: 15907372
  47. Cell cycle-dependent regulation of yeast telomerase by Ku.
    Nat Struct Mol Biol. 2004 Dec;11(12):1198-205 PMID: 15531893
  48. Functional domains of the yeast splicing factor Prp22p.
    J Biol Chem. 2001 Jun 15;276(24):21184-91 PMID: 11283007
  49. Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends.
    Genes Dev. 2003 Oct 1;17(19):2384-95 PMID: 12975323
  50. Roles of the Bloom's syndrome helicase in the maintenance of genome stability.
    Biochem Soc Trans. 2005 Dec;33(Pt 6):1456-9 PMID: 16246145
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl561
Email
[email protected]
Published
2006-00-00
Epub
2006-00-25
Pages
4147-53
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1616966
Subset
IM
Grants
NIGMS NIH HHS · GM43265 · United States
NIGMS NIH HHS · R01 GM043265 · United States
NIGMS NIH HHS · GM26938 · United States
NIGMS NIH HHS · R37 GM026938 · United States
NIGMS NIH HHS · R01 GM026938 · United States
External Links
PubMed source DOI: 10.1093/nar/gkl561 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2