Skip to main content

Overview: What Are Helicases?

  • Chapter
  • First Online:
DNA Helicases and DNA Motor Proteins

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 767))

Abstract

First discovered in the 1970s, DNA helicases were initially described as enzymes that use chemical energy to separate (i.e., to unwind) the complementary strands of DNA. Because helicases are ubiquitous, display a range of fascinating biochemical activities, and are involved in all aspects of DNA metabolism, defects in human helicases are linked to a variety of genetic disorders, and helicase research continues to be important in understanding the molecular basis of DNA replication, recombination, and repair. The purpose of this book is to organize this information and to update the traditional view of these enzymes, because it is now evident that not all helicases possess bona fide strand separation activity and may function instead as energy-dependent switches or translocases. In this chapter, we will first discuss the biochemical and structural features of DNA—the lattice on which helicases operate—and its cellular organization. We will then provide a historical overview of helicases, starting from their discovery and classification, leading to their structures, mechanisms, and biomedical significance. Finally, we will highlight several key advances and developments in helicase research, and summarize some remaining questions and active areas of investigation. The subsequent chapters will discuss these topics and others in greater detail and are written by experts of these respective fields.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Watson JD, Crick FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953;171(4356):737–8.

    Article  CAS  Google Scholar 

  2. Meselson M, Stahl FW. The replication of DNA in Escherichia coli. Proc Natl Acad Sci U S A. 1958;44(7):671–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Andrews AJ, Luger K. Nucleosome structure(s) and stability: variations on a theme. Annu Rev Biophys. 2011;40:99–117.

    CAS  PubMed  Google Scholar 

  4. Abdel-Monem M, Durwald H, Hoffmann-Berling H. Enzymic unwinding of DNA. 2. Chain separation by an ATP-dependent DNA unwinding enzyme. Eur J Biochem. 1976;65(2):441–9.

    CAS  PubMed  Google Scholar 

  5. Abdel-Monem M, Hoffmann-Berling H. Enzymatic unwinding of DNA. 1. Purification and characterization of a DNA-dependent ATPase from Escherichia coli. Eur J Biochem. 1976;65(2):431–40.

    CAS  PubMed  Google Scholar 

  6. Gorbalenya AE, Koonin EV. Helicases: amino acid sequence comparisons and structure-function relationships. Curr Opin Struct Biol. 1993;3:419–29.

    CAS  Google Scholar 

  7. Singleton MR, Dillingham MS, Wigley DB. Structure and mechanism of helicases and nucleic acid translocases. Annu Rev Biochem. 2007;76:23–50.

    CAS  PubMed  Google Scholar 

  8. Jankowsky E, Fairman ME. RNA helicases—one fold for many functions. Curr Opin Struct Biol. 2007;17(3):316–24.

    CAS  PubMed  Google Scholar 

  9. Jankowsky E, Fairman ME, Yang Q. RNA helicases: versatile ATP-driven nanomotors. J Nanosci Nanotechnol. 2005;5(12):1983–9.

    CAS  PubMed  Google Scholar 

  10. Brendza KM, et al. Autoinhibition of Escherichia coli Rep monomer helicase activity by its 2B subdomain. Proc Natl Acad Sci U S A. 2005;102(29):10076–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Maluf NK, Fischer CJ, Lohman TM. A dimer of Escherichia coli UvrD is the active form of the helicase in vitro. J Mol Biol. 2003;325(5):913–35.

    CAS  PubMed  Google Scholar 

  12. Niedziela-Majka A, et al. Bacillus stearothermophilus PcrA monomer is a single-stranded DNA translocase but not a processive helicase in vitro. J Biol Chem. 2007;282(37): 27076–85.

    CAS  PubMed  Google Scholar 

  13. Tomko EJ, et al. A nonuniform stepping mechanism for E. coli UvrD monomer translocation along single-stranded DNA. Mol Cell. 2007;26(3):335–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Park SK, et al. RNA helicase activity of Escherichia coli SecA protein. Biochem Biophys Res Commun. 1997;235:593–7.

    CAS  PubMed  Google Scholar 

  15. Gelis I, et al. Structural basis for signal-sequence recognition by the translocase motor SecA as determined by NMR. Cell. 2007;131(4):756–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Martin A, Baker TA, Sauer RT. Rebuilt AAA+ motors reveal operating principles for ATP-fuelled machines. Nature. 2005;437(7062):1115–20.

    CAS  PubMed  Google Scholar 

  17. Lohman TM, Bjornson KP. Mechanisms of helicase-catalyzed DNA unwinding. Annu Rev Biochem. 1996;65:169–214.

    CAS  PubMed  Google Scholar 

  18. Patel SS, Donmez I. Mechanisms of helicases. J Biol Chem. 2006;281(27):18265–8.

    CAS  PubMed  Google Scholar 

  19. Schnitzer MJ, Block SM. Kinesin hydrolyses one ATP per 8-nm step. Nature. 1997;388: 386–90.

    CAS  PubMed  Google Scholar 

  20. Cheng W, et al. Single-base pair unwinding and asynchronous RNA release by the hepatitis C virus NS3 helicase. Science. 2011;333(6050):1746–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lucius AL, et al. General methods for analysis of sequential “n-step” kinetic mechanisms: application to single turnover kinetics of helicase-catalyzed DNA unwinding. Biophys J. 2003;85(4):2224–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Bianco PR, et al. Processive translocation and DNA unwinding by individual RecBCD enzyme molecules. Nature. 2001;409:374–8.

    CAS  PubMed  Google Scholar 

  23. Sikora B, et al. DNA unwinding by Escherichia coli DNA helicase I (TraI) provides evidence for a processive monomeric molecular motor. J Biol Chem. 2006;281(47):36110–6.

    CAS  PubMed  Google Scholar 

  24. Spies M, et al. RecBCD enzyme switches lead motor subunits in response to chi recognition. Cell. 2007;131(4):694–705.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Betterton MD, Julicher F. Opening of nucleic-acid double strands by helicases: active versus passive opening. Phys Rev E Stat Nonlin Soft Matter Phys. 2005;71(1):011904.

    CAS  PubMed  Google Scholar 

  26. Delagoutte E, von Hippel PH. Helicase mechanisms and the coupling of helicases within macromolecular machines. Part I: structures and properties of isolated helicases. Q Rev Biophys. 2002;35(4):431–78.

    CAS  PubMed  Google Scholar 

  27. Johnson DS, et al. Single-molecule studies reveal dynamics of DNA unwinding by the ring-shaped T7 helicase. Cell. 2007;129(7):1299–309.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Manosas M, et al. Active and passive mechanisms of helicases. Nucleic Acids Res. 2010;38(16):5518–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Byrd AK, et al. Dda helicase tightly couples translocation on single-stranded DNA to unwinding of duplex DNA: Dda is an optimally active helicase. J Mol Biol. 2012;420(3):141–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Singleton MR, et al. Crystal structure of RecBCD enzyme reveals a machine for processing DNA breaks. Nature. 2004;432(7014):187–93.

    CAS  PubMed  Google Scholar 

  31. Farah JA, Smith GR. The RecBCD enzyme initiation complex for DNA unwinding: enzyme positioning and DNA opening. J Mol Biol. 1997;272:699–715.

    CAS  PubMed  Google Scholar 

  32. Wong CJ, Lucius AL, Lohman TM. Energetics of DNA end binding by E. coli RecBC and RecBCD helicases indicate loop formation in the 3′-single-stranded DNA tail. J Mol Biol. 2005;352(4):765–82.

    CAS  PubMed  Google Scholar 

  33. Wu CG, Bradford C, Lohman TM. Escherichia coli RecBC helicase has two translocase activities controlled by a single ATPase motor. Nat Struct Mol Biol. 2010;17(10):1210–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ahnert P, Patel SS. Asymmetric interactions of hexameric bacteriophage T7 DNA helicase with the 5′- and 3′-tails of the forked DNA substrate. J Biol Chem. 1997;272(51):32267–73.

    CAS  PubMed  Google Scholar 

  35. Hacker KJ, Johnson KA. A hexameric helicase encircles one DNA strand and excludes the other during DNA unwinding. Biochemistry. 1997;36:14080–7.

    CAS  PubMed  Google Scholar 

  36. Galletto R, Jezewska MJ, Bujalowski W. Unzipping mechanism of the double-stranded DNA unwinding by a hexameric helicase: the effect of the 3′ arm and the stability of the dsDNA on the unwinding activity of the Escherichia coli DnaB helicase. J Mol Biol. 2004;343(1):101–14.

    CAS  PubMed  Google Scholar 

  37. Eoff RL, Raney KD. Helicase-catalysed translocation and strand separation. Biochem Soc Trans. 2005;33(Pt 6):1474–8.

    CAS  PubMed  Google Scholar 

  38. Pugh RA, Wu CG, Spies M. Regulation of translocation polarity by helicase domain 1 in SF2B helicases. EMBO J. 2012;31(2):503–14.

    CAS  PubMed  Google Scholar 

  39. Saikrishnan K, et al. DNA binding to RecD: role of the 1B domain in SF1B helicase activity. EMBO J. 2008;27(16):2222–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Tomishige M, Stuurman N, Vale RD. Single-molecule observations of neck linker conformational changes in the kinesin motor protein. Nat Struct Mol Biol. 2006;13(10):887–94.

    CAS  PubMed  Google Scholar 

  41. Kuper J, et al. Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation. EMBO J. 2012;31(2):494–502.

    CAS  PubMed  Google Scholar 

  42. Cantor SB, et al. BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell. 2001;105(1):149–60.

    CAS  PubMed  Google Scholar 

  43. Clapperton JA, et al. Structure and mechanism of BRCA1 BRCT domain recognition of ­phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol. 2004;11(6):512–8.

    CAS  PubMed  Google Scholar 

  44. Kuhn B, Abdel-Monem M, Hoffmann-Berling H. DNA helicases. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 1):63–7.

    CAS  PubMed  Google Scholar 

  45. Venkatesan M, Silver LL, Nossal NG. J Biol Chem. 1982;257:12426–34.

    CAS  PubMed  Google Scholar 

  46. Matson SW, Tabor S, Richardson CC. The gene 4 protein of bacteriophage T7. Characterization of helicase activity. J Biol Chem. 1983;258:14017–24.

    CAS  PubMed  Google Scholar 

  47. Dillingham MS, et al. Fluorescent single-stranded DNA binding protein as a probe for sensitive, real-time assays of helicase activity. Biophys J. 2008;95(7):3330–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Eggleston AK, Rahim NA, Kowalczykowski SC. A helicase assay based on the displacement of fluorescent, nucleic acid-binding ligands. Nucleic Acids Res. 1996;24:1179–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Ali JA, Lohman TM. Kinetic measurement of the step size of DNA unwinding by Escherichia coli UvrD helicase. Science. 1997;275(5298):377–80.

    CAS  PubMed  Google Scholar 

  50. Yodh JG, Schlierf M, Ha T. Insight into helicase mechanism and function revealed through single-molecule approaches. Q Rev Biophys. 2010;43(2):185–217.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Comstock MJ, Ha T, Chemla YR. Ultrahigh-resolution optical trap with single-fluorophore sensitivity. Nat Methods. 2011;8(4):335–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Dessinges MN, et al. Stretching single stranded DNA, a model polyelectrolyte. Phys Rev Lett. 2002;89(24):248102.

    PubMed  Google Scholar 

  53. Perkins TT, et al. Forward and reverse motion of single RecBCD molecules on DNA. Biophys J. 2004;86(3):1640–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Spies M, et al. A molecular throttle: the recombination hotspot chi controls DNA translocation by the RecBCD helicase. Cell. 2003;114(5):647–54.

    CAS  PubMed  Google Scholar 

  55. Sun B, et al. ATP-induced helicase slippage reveals highly coordinated subunits. Nature. 2011;478(7367):132–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Fazio TA, et al. Fabrication of nanoscale “curtain rods” for DNA curtains using nanoimprint lithography. J Vac Sci Technol A. 2009;27(6):3095–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Fazio T, et al. DNA curtains and nanoscale curtain rods: high-throughput tools for single ­molecule imaging. Langmuir. 2008;24(18):10524–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Finkelstein IJ, Visnapuu ML, Greene EC. Single-molecule imaging reveals mechanisms of protein disruption by a DNA translocase. Nature. 2010;468(7326):983–7.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Spies .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wu, C.G., Spies, M. (2013). Overview: What Are Helicases?. In: Spies, M. (eds) DNA Helicases and DNA Motor Proteins. Advances in Experimental Medicine and Biology, vol 767. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5037-5_1

Download citation

Publish with us

Policies and ethics