Highly thermostable RadA protein from the archaeon Pyrococcus woesei enhances specificity of simplex and multiplex PCR assays

J Appl Genet. 2016 May;57(2):239-49. doi: 10.1007/s13353-015-0314-5. Epub 2015 Sep 4.

Abstract

The radA gene of the hyperthermophilic archaeon Pyrococcus woesei (Thermococcales) was cloned and overexpressed in Escherichia coli. The 1050-bp gene codes for a 349-amino-acid polypeptide with an M r of 38,397 which shows 100 % positional amino acid identity to Pyrococcus furiosus RadA and 27.1 % to the E. coli RecA protein. Recombinant RadA was overproduced in Escherichia coli as a His-tagged fusion protein and purified to electrophoretic homogeneity using a simple procedure consisting of ammonium sulfate precipitation and metal-affinity chromatography. In solution RadA exists as an undecamer (11-mer). The protein binds both to ssDNA and dsDNA. RadA has been found to be highly thermostable, it remains almost unaffected by a 4-h incubation at 94 °C. The addition of the RadA protein to either simplex or multiplex PCR assays, significantly improves the specificity of DNA amplification by eliminating non-specific products. Among applications tested the RadA protein proved to be useful in allelic discrimination assay of HADHA gene associated with long-chain 3-hydroxylacyl-CoA dehydrogenase deficiency that in infancy may lead to hypotonia, serious heart and liver problems and even sudden death.

Keywords: Hyperthermophiles; RecA; Thermal stability; Thermococcales.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Cloning, Molecular
  • DNA, Archaeal / genetics
  • DNA, Single-Stranded / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Hot Temperature
  • Molecular Sequence Data
  • Multiplex Polymerase Chain Reaction*
  • Protein Stability
  • Pyrococcus / enzymology
  • Pyrococcus / genetics*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Archaeal Proteins
  • DNA, Archaeal
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • RadA protein, archaeal
  • Recombinant Proteins