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.
Bibliographical noteFunding Information:
National Research Foundation (NRF) of Korea [NRF-2019R1A2C1089808, IBS-R023-D1]; S.H.K. and S.-C. H. also acknowledge the Global Research &Development Center Program [2018K1A4A3A01064272] through the NRF funded by the Ministry of Science and ICT. N.-K.L. acknowledges a NRF grant [NRF-2020R1A2B5B01002041]. Funding for open access charge: vNRF [NRF-2019R1A2C1089808].
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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