Measurement of steady-state kinetic parameters for DNA unwinding by the bacteriophage T4 Dda helicase: use of peptide nucleic acids to trap single-stranded DNA products of helicase reactions

Nucleic Acids Res. 2001 Jul 1;29(13):2829-35. doi: 10.1093/nar/29.13.2829.

Abstract

Measurement of steady-state rates of unwinding of double-stranded oligonucleotides by helicases is hampered due to rapid reannealing of the single-stranded DNA products. Including an oligonucleotide in the reaction mixture which can hybridize with one of the single strands can prevent reannealing. However, helicases bind to single-stranded DNA, therefore the additional oligonucleotide can sequester the enzyme, leading to slower observed rates for unwinding. To circumvent this problem, the oligonucleotide that serves as a trap was replaced with a strand of peptide nucleic acid (PNA). Fluorescence polarization was used to determine that a 15mer PNA strand does not bind to the bacteriophage T4 Dda helicase. Steady-state kinetic parameters of unwinding catalyzed by Dda were determined by using PNA as a trapping strand. The substrate consisted of a partial duplex with 15 nt of single-stranded DNA and 15 bp. In the presence of 250 nM substrate and 1 nM Dda, the rate of unwinding in the presence of the DNA trapping strand was 0.30 nM s(-1) whereas the rate was 1.34 nM s(-1) in the presence of the PNA trapping strand. PNA prevents reannealing of single-stranded DNA products, but does not sequester the helicase. This assay will prove useful in defining the complete kinetic mechanism for unwinding of oligonucleotide substrates by this helicase.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Bacteriophage T4 / enzymology*
  • Base Pairing
  • Base Sequence
  • Catalysis
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism*
  • DNA Helicases / metabolism*
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism
  • Fluorescence Polarization
  • Kinetics
  • Nucleic Acid Conformation*
  • Nucleic Acid Denaturation
  • Nucleic Acid Hybridization
  • Peptide Nucleic Acids / chemistry
  • Peptide Nucleic Acids / genetics
  • Peptide Nucleic Acids / metabolism
  • Protein Binding
  • Viral Proteins*

Substances

  • DNA, Single-Stranded
  • Peptide Nucleic Acids
  • Viral Proteins
  • Adenosine Triphosphate
  • DNA
  • DNA Helicases
  • dda DNA helicase protein, Bacteriophage T4