Insight into formation propensity of pseudocircular DNA G-hairpins

0542802 - BFÚ 2022 RIV GB eng J - Journal Article
Zivkovic, M.L. - Gajarský, M. - Bekova, K. - Stadlbauer, Petr - Vicherek, L. - Petrová, Magdalena - Fiala, R. - Rosenberg, Ivan - Šponer, Jiří - Plavec, J. - Trantírek, L.
Insight into formation propensity of pseudocircular DNA G-hairpins.
Nucleic Acids Research. Roč. 49, č. 4 (2021), s. 2317-2332. ISSN 0305-1048. E-ISSN 1362-4962
R&D Projects: GA ČR(CZ) GA17-12703S; GA MŠMT EF15_003/0000477
Institutional support: RVO:68081707 ; RVO:61388963
Keywords : molecular-dynamics simulations * g-quadruplex structure * amber force-field * g-triplex * folding pathways
OECD category: Biochemistry and molecular biology; Biochemistry and molecular biology (UOCHB-X)
Impact factor: 19.160, year: 2021
Method of publishing: Open access
https://academic.oup.com/nar/article/49/4/2317/6125665

We recently showed that Saccharomyces cerevisiae telomeric DNA can fold into an unprecedented pseudocircular G-hairpin (PGH) structure. However, the formation of PGHs in the context of extended sequences, which is a prerequisite for their function in vivo and their applications in biotechnology, has not been elucidated. Here, we show that despite its 'circular' nature, PGHs tolerate single-stranded (ss) protrusions. High-resolution NMR structure of a novel member of PGH family reveals the atomistic details on a junction between ssDNA and PGH unit. Identification of new sequences capable of folding into one of the two forms of PGH helped in defining minimal sequence requirements for their formation. Our time-resolved NMR data indicate a possibility that PGHs fold via a complex kinetic partitioning mechanism and suggests the existence of K+ ion-dependent PGH folding intermediates. The data not only provide an explanation of cation-type-dependent formation of PGHs, but also explain the unusually large hysteresis between PGH melting and annealing noted in our previous study. Our findings have important implications for DNA biology and nanotechnology. Overrepresentation of sequences able to form PGHs in the evolutionary-conserved regions of the human genome implies their functionally important biological role(s).
Permanent Link: http://hdl.handle.net/11104/0320148