Chesnokov's review catalogs the full alphabet of DNA helical forms (A, Aβ², B, Ξ±-Bβ², Ξ²-Bβ², C, Cβ², Cβ³, D, E, Z), grounded in classic fiber X-ray diffraction, circular dichroism, and infrared linear dichroism studies . The strongest quantitative content is Table 1 on the BβZ transition, showing that cytosine methylation (dmβ΅C) dramatically lowers the ionic threshold β a central epigenetic-relevance argument .
The review's framing of BβZ energetics is consistent with modern thermodynamic work showing base stacking, not base pairing, predominantly stabilizes the duplex . Its picture of B-DNA as a dynamic, 'breathing' structure is directly supported by microsecond MD showing transient base-pair opening (~10β20 ps lifetimes) and ~15% BII subpopulations .
The review hedges on in vivo Z-DNA; subsequent work has substantially strengthened that question. Z-DNA was later shown to be an intrinsic, nuclease-resistant component of neutrophil extracellular traps (~20% of extracellular DNA signal) tunable back to B-DNA by chloroquine , and ultrahigh-resolution (0.78 Γ ) Z-DNA crystallography revealed extensive alternate backbone conformations the review does not anticipate .
Key weaknesses: (1) it is a literature synthesis with no new data, relying heavily on 1970sβ1980s fiber experiments whose conditions do not map cleanly onto cellular environments; (2) the claim that natural DNA structure is sequence-independent sits awkwardly with modern sequence-dependent stacking energetics ; (3) no direct in vivo structural validation is presented β the polytene-chromosome antibody data it cites are indirect. The BβZ regulatory hypothesis it advances would be falsified if in vivo assays consistently fail to detect stabilized Z-DNA at physiological conditions or any expression coupling .
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