Sequence-dependent cost for Z-form shapes the torsion-driven B–Z transition via close interplay of Z-DNA and DNA bubble

• Published in: Nucleic acids research 2021-04, Vol.49 (7), p.3651-3660
• Main Authors: Kim, Sook Ho, Jung, Hae Jun, Lee, Il-Buem, Lee, Nam-Kyung, Hong, Seok-Cheol
• Format: Article
• Language: English
• Subjects: Chemical Biology and Nucleic Acid Chemistry; DNA, B-Form - chemistry; DNA, Z-Form - chemistry; Kinetics; Microsatellite Repeats; Models, Chemical; Models, Molecular; Models, Statistical; Repetitive Sequences, Nucleic Acid; Thermodynamics
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkab153

Abstract Despite recent genome-wide investigations of functional DNA elements, the mechanistic details about their actions remain elusive. One intriguing possibility is that DNA sequences with special patterns play biological roles, adopting non-B-DNA conformations. Here we investigated dynamics of thymine-guanine (TG) repeats, microsatellite sequences and recurrently found in promoters, as well as cytosine–guanine (CG) repeats, best-known Z-DNA forming sequence, in the aspect of Z-DNA formation. We measured the energy barriers of the B–Z transition with those repeats and discovered the sequence-dependent penalty for Z-DNA generates distinctive thermodynamic and kinetic features in the torque-induced transition. Due to the higher torsional stress required for Z-form in TG repeats, a bubble could be induced more easily, suppressing Z-DNA induction, but facilitate the B–Z interconversion kinetically at the transition midpoint. Thus, the Z-form by TG repeats has advantages as a torsion buffer and bubble selector while the Z-form by CG repeats likely behaves as torsion absorber. Our statistical physics model supports quantitatively the populations of Z-DNA and reveals the pivotal roles of bubbles in state dynamics. All taken together, a quantitative picture for the transition was deduced within the close interplay among bubbles, plectonemes and Z-DNA. Graphical Abstract Graphical Abstract Dynamic interplay of bubble, supercoil and twisted B-DNA with the Z-DNA state of CG or TG repeats detected by smFRET under various mechanical (force and σ) conditions imposed by magnetic tweezers. TG repeats exhibit higher B–Z transition rates (k) than CG repeats at their respective midpoint σ values.