Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 9, Pages 5024-5036Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa225
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Funding
- Spanish Ministry of Economy and Competitiveness [CEX2018-000805-M, MAT2017-83273-R, BFU2017-83794-P, PGC2018-099341-B-I00]
- Comunidad de Madrid [NanoMagCOST P2018 INMT-4321, Tec4Bio - S2018/NMT-4443, NanoBioCancer - Y2018/BIO-4747]
- European Research Council (ERC) under the European Union Horizon 2020 research and innovation [681299]
- Marie Sklodowska Curie Fellowship within the Horizons 2020 framework [DLV-795286]
- International PhD Program of 'La Caixa-Severo Ochoa'
- Competitiveness and Industry Ministry of a FPI fellowship [BES-2015-071244]
- European Research Council
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A-tracts are A:T rich DNA sequences that exhibit unique structural and mechanical properties associated with several functions in vivo. The crystallographic structure of A-tracts has been well characterized. However, the mechanical properties of these sequences is controversial and their response to force remains unexplored. Here, we rationalize the mechanical properties of in-phase A-tracts present in the Caenorhabditis elegans genome over a wide range of external forces, using single-molecule experiments and theoretical polymer models. Atomic Force Microscopy imaging shows that A-tracts induce long-range (similar to 200 nm) bending, which originates from an intrinsically bent structure rather than from larger bending flexibility. These data are well described with a theoretical model based on the worm-like chain model that includes intrinsic bending. Magnetic tweezers experiments show that the mechanical response of A-tracts and arbitrary DNA sequences have a similar dependence with monovalent salt supporting that the observed A-tract bend is intrinsic to the sequence. Optical tweezers experiments reveal a high stretch modulus of the A-tract sequences in the enthalpic regime. Our work rationalizes the complex multiscale flexibility of A-tracts, providing a physical basis for the versatile character of these sequences inside the cell.
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