Base sequence criteria and Cartesian coordinates for stable B/Z and B/Z/B junctions in relaxed DNA.

Area of Science:

• Molecular Biology
• Biophysics
• Genetics

Background:

• The Z-form DNA, a left-handed double helix, is proposed to exist in short segments within the genome.
• Understanding the transition between B-form and Z-form DNA is crucial for comprehending its biological roles.

Purpose of the Study:

• To determine the minimum length of alternating CG sequences required for Z-form DNA formation within a B-form DNA context.
• To investigate the structure and thermodynamics of the B/Z DNA junction.

Main Methods:

• Synthesis of self-complementary oligomers with alternating CG sequences.
• Conformational analysis using Raman spectroscopy in high salt conditions.
• Isotopic H/D exchange experiments and thermodynamic analysis.

Main Results:

• A minimum of 12 alternating CG base pairs is necessary to stabilize the Z-form within a B-form DNA duplex.
• Only the central 4 CG base pairs transition to the Z-form, flanked by B-form regions.
• A B/Z junction model with direct helix flipping and no base pairs at the junction was proposed and supported by experimental data.

Conclusions:

• The B/Z DNA junction involves a direct transition between helical forms, nucleated by AT pairs and propagating into CG sequences.
• The enthalpy of B/Z junction formation is approximately +16 kcal/junction.
• Molecular modeling provides insights into the structural details of B/Z and B/Z/B junctions.