DNA microarrays with unimolecular hairpin double-stranded DNA probes: fabrication and exploration of sequence-specific DNA/protein interactions

J Biochem Biophys Methods. 2003 Mar 28;55(3):215-32. doi: 10.1016/s0165-022x(03)00048-4.

Abstract

We have fabricated double-stranded DNA (dsDNA) microarrays containing unimolecular hairpin dsDNA probes immobilized on glass slides. The unimolecular hairpin dsDNA microarrays were manufactured by four steps: Firstly, synthesizing single-stranded DNA (ssDNA) oligonucleotides with two reverse-complementary sequences at 3' hydroxyl end and an overhang sequence at 5' amino end. Secondly, microspotting ssDNA on glutaraldehyde-derived glass slide to form ssDNA microarrays. Thirdly, annealing two reverse-complementary sequences to form hairpin primer at 3' end of immobilized ssDNA and thus to create partial-dsDNA microarray. Fourthly, enzymatically extending hairpin primer to convert partial-dsDNA microarrays into complete-dsDNA microarray. The excellent efficiency and high accuracy of the enzymatic synthesis were demonstrated by incorporation of fluorescently labeled dUTPs in Klenow extension and digestion of dsDNA microarrays with restriction endonuclease. The accessibility and specificity of the DNA-binding proteins binding to dsDNA microarrays were verified by binding Cy3-labeled NF-kappaB to dsDNA microarrays. The dsDNA microarrays have great potential to provide a high-throughput platform for investigation of sequence-specific DNA/protein interactions involved in gene expression regulation, restriction and so on.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Binding Sites
  • DNA / chemistry*
  • DNA Probes / chemical synthesis*
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Equipment Design
  • Equipment Failure Analysis
  • Feasibility Studies
  • Oligonucleotide Array Sequence Analysis / instrumentation*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Protein Array Analysis / instrumentation*
  • Protein Array Analysis / methods*
  • Protein Binding
  • Sequence Analysis, DNA / instrumentation
  • Sequence Analysis, DNA / methods

Substances

  • DNA Probes
  • DNA-Binding Proteins
  • DNA