4.7 Article

The Binding of Monoclonal and Polyclonal Anti-Z-DNA Antibodies to DNA of Various Species Origin

Journal

Publisher

MDPI
DOI: 10.3390/ijms22168931

Keywords

DNA; Z-DNA; B-DNA; immunoassay; anti-DNA antibodies; conformation; helix; phosphodiester backbone

Funding

  1. Veterans Administration Merit Review grant [BX003772]
  2. National Institutes of Health grant [R01AR073935]

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DNA can have different backbone conformations, with Z-DNA being a left-handed helix with a zig-zag orientation depending on base sequence, modification, and supercoiling. Experimental results demonstrate that anti-Z-DNA antibodies can serve as probes for detecting the presence of Z-DNA in DNA.
DNA is a polymeric macromolecule that can display a variety of backbone conformations. While the classical B-DNA is a right-handed double helix, Z-DNA is a left-handed helix with a zig-zag orientation. The Z conformation depends upon the base sequence, base modification and supercoiling and is considered to be transient. To determine whether the presence of Z-DNA can be detected immunochemically, the binding of monoclonal and polyclonal anti-Z-DNA antibodies to a panel of natural DNA antigens was assessed by an ELISA using brominated poly(dG-dC) as a control for Z-DNA. As these studies showed, among natural DNA tested (Micrococcus luteus, calf thymus, Escherichia coli, salmon sperm, lambda phage), micrococcal (MC) DNA showed the highest binding with both anti-Z-DNA preparations, and E. coli DNA showed binding with the monoclonal anti-DNA preparation. The specificity for Z-DNA conformation in MC DNA was demonstrated by an inhibition binding assay. An algorithm to identify propensity to form Z-DNA indicated that DNA from Mycobacterium tuberculosis could form Z-DNA, a prediction confirmed by immunoassay. Together, these findings indicate that anti-Z-DNA antibodies can serve as probes for the presence of Z-DNA in DNA of various species origin and that the content of Z-DNA varies significantly among DNA sources.

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