A molecular view of DNA flexibility

Abstract

DNA dynamics can only be understood by taking into account its complex mechanical behavior at different length scales. At the micrometer level, the mechanical properties of single DNA molecules have been well-characterized by polymer models and are commonly quantified by a persistence length of 50 nm (~150 bp). However, at the base pair level (~3.4 Å), the dynamics of DNA involves complex molecular mechanisms that are still being deciphered. Here, we review recent single-molecule experiments and molecular dynamics simulations that are providing novel insights into DNA mechanics from such a molecular perspective. We first discuss recent findings on sequence-dependent DNA mechanical properties, including sequences that resist mechanical stress and sequences that can accommodate strong deformations. We then comment on the intricate effects of cytosine methylation and DNA mismatches on DNA mechanics. Finally, we review recently reported differences in the mechanical properties of DNA and double-stranded RNA, the other double-helical carrier of genetic information. A thorough examination of the recent single-molecule literature permits establishing a set of general ‘rules’ that reasonably explain the mechanics of nucleic acids at the base pair level. These simple rules offer an improved description of certain biological systems and might serve as valuable guidelines for future design of DNA and RNA nanostructures.

Deciphering the mechanical properties of B‐DNA duplex

“…A review on DNA flexibility has recently been published by Marin‐Gonzalez et al 52 The authors cover a broad range of topics including the effect of chemical modifications, mismatches, transition between B and Z forms, or comparison to dsRNA. By contrast, in this work we mostly focus on structurally intact, chemically unmodified DNA in its B‐form.…”

Sequence-Specific Features of Short Double-Strand, Blunt-End RNAs Have RIG-I- and Type 1 Interferon-Dependent or -Independent Anti-Viral Effects

“…miR29b-1* mimic contains a centrally positioned AUAU-motif, which constitutes a 4 bp-long AU-tract, i.e., dsRNA sequences of alternating adenines and uracils. Molecular dynamics simulations and atomic force microscopy (AFM) have indicated that dsRNA AU-tracts induce a bend in the molecule due to a local compression of the major groove [ 62 , 75 ]. Such bend has been detected also in miR29b-1* [ 62 ].…”

“…Accordingly, the antiviral effects of the dsRNA miR29b-1* mimic were sequence-dependent, although the essential features of the sequence motifs necessary to activate RIG-I are still unclear. Interestingly, molecular dynamics simulations indicate that AU-tract motives in the context of GC-rich sequences give rise to dsRNA bending, owing to the collapse of the major groove located away from the sugar backbone, likely due to the lack of a hydrogen bond in AU compared to GC base pairs [ 62 , 75 ]. Additional simulations showed that changes in the major groove widths are correlated to minor groove changes by distinct geometrical alterations in the base pairs [ 100 ].…”

Bending of Canonical and G/T Mismatched DNAs

“…MMR overall effectivity is proportional to the affinity of MutS to mismatched DNA, but some studies suggest that it is not the sole determinant in the efficiency of mismatch repair . While available data provided a general understanding of error recognition, − individual mechanical factors responsible for its high efficacy are not fully understood. , …”

“…6 While available data provided a general understanding of error recognition, 7−12 individual mechanical factors responsible for its high efficacy are not fully understood. 13,14 MutS is a clamp-like dimer that encircles DNA and seeks errors along the double helix. 10,16 Published crystal structures showed how MutS captures a single nucleotide mismatch 11,17−23 and IDLs.…”