Biophysical characterization of the association of histones with single-stranded DNA

Wang, Ying; Merwyk, Luis van; Tönsing, Katja; Walhorn, Volker; Anselmetti, Dario; Fernàndez‐Busquets, Xavier

doi:10.1016/j.bbagen.2017.07.018

Cited by 7 publications

(5 citation statements)

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“…1 b). In contrast, a multiple rotation of a nicked dsDNA molecule causes no under- or overwinding since the single strand can rotate around the phosphodiester bond in idle state [ 48 ]. Such structural characteristics of dsDNA polymers can be used to study dsDNA unwinding induced by drug-intercalation.…”

Section: Resultsmentioning

confidence: 99%

Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers

et al. 2018

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BackgroundChemotherapeutic agents (anti-cancer drugs) are small cytostatic or cytotoxic molecules that often bind to double-stranded DNA (dsDNA) resulting in modifications of their structural and nanomechanical properties and thus interfering with the cell proliferation process.MethodsWe investigated the anthraquinone compound mitoxantrone that is used for treating certain cancer types like leukemia and lymphoma with magnetic tweezers as a single molecule nanosensor. In order to study the association of mitoxantrone with dsDNA, we conducted force-extension and mechanical overwinding experiments with a sensitivity of 10−14 N.ResultsUsing this method, we were able to estimate an equilibrium constant of association Ka ≈ 1 × 105 M−1 as well as a binding site size of n ≈ 2.5 base pairs for mitoxantrone. An unwinding angle of mitoxantrone-intercalation of ϑ ≈ 16° was determined.ConclusionMoreover, we observed a complex concentration-dependent bimodal binding behavior, where mitoxantrone associates to dsDNA as an intercalator and groove binder simultaneously at low concentrations and as a mere intercalator at high concentrations.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0381-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers

et al. 2018

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“…Replication protein A complex (RPA, a complex that binds and protects single strand DNA), can also function as a binding partner for an H3–H4 dimer [55]. Possibly related to these findings, recent studies have speculated that histones may stably interact with single-stranded DNA [88,89]. Whether this is mediated through their interaction with RPA, and what role this would have in vivo (perhaps protecting the lagging strand or conserving the original nucleosome position), is yet to be solidified.…”

Section: Histone Recycling During Replicationmentioning

confidence: 99%

The histone chaperoning pathway: from ribosome to nucleosome

Pardal

Fernandes-Duarte

Bowman

2019

Essays in Biochemistry

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Nucleosomes represent the fundamental repeating unit of eukaryotic DNA, and comprise eight core histones around which DNA is wrapped in nearly two superhelical turns. Histones do not have the intrinsic ability to form nucleosomes; rather, they require an extensive repertoire of interacting proteins collectively known as ‘histone chaperones’. At a fundamental level, it is believed that histone chaperones guide the assembly of nucleosomes through preventing non-productive charge-based aggregates between the basic histones and acidic cellular components. At a broader level, histone chaperones influence almost all aspects of chromatin biology, regulating histone supply and demand, governing histone variant deposition, maintaining functional chromatin domains and being co-factors for histone post-translational modifications, to name a few. In this essay we review recent structural insights into histone-chaperone interactions, explore evidence for the existence of a histone chaperoning ‘pathway’ and reconcile how such histone-chaperone interactions may function thermodynamically to assemble nucleosomes and maintain chromatin homeostasis.

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“…The percentage of L-DNA induced by torsion increases linearly with σ , until the critical value of n t,max -800, or σ max −1.8, where all B-DNA is converted to L-DNA. At the two extremes (n t =0 or σ =0 and n t,max −800 or σ max -1.8), the DNA extension, L eB and L eL , respectively, is correctly modelled as a function of the external force F, by a classical Worm Like Chain (WLC) (38,39,40) with the corresponding L 0B , L pB and L 0L , L pL for pure B and L-DNA, respectively (41). The relation between F and both L eB and L eL is described by the function f given by the classical WLC model as follows: From which, it is possible to calculate the DNA extension as L eB = f - 1 ( F , L pB , L 0 B ) and L eL = f - 1 ( F , L pL , L 0 L ).…”

Section: Resultsmentioning

confidence: 99%

Nanomechanics of negatively supercoiled diaminopurine-substituted DNA

Salerno

Mantegazza

Cassina

et al. 2021

Preprint

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Single molecule experiments have demonstrated a progressive transition from a B- to an L-form helix as DNA is gently stretched and progressively unwound. Since the particular sequence of a DNA segment influences both base stacking and hydrogen bonding, the conformational dynamics of B-to-L transitions should be tunable. To test this idea, DNA with diaminopurine replacing adenine was synthesized to produce linear fragments with triply hydrogen-bonded A:T base pairs. Triple hydrogen bonding stiffened the DNA by 30% flexurally. In addition, DAP-substituted DNA formed plectonemes with larger gyres for both B- and L-form helices. Both unmodified and DAP-substituted DNA transitioned from a B- to an L-helix under physiological conditions of mild tension and unwinding. This transition avoids writhing by DNA stretched and unwound by enzymatic activity. The intramolecular nature and ease of this transition likely prevent cumbersome topological rearrangements in genomic DNA that would require topoisomerase activity to resolve. L-DNA displayed about tenfold lower persistence length indicating it is much more contractile and prone to sharp bends and kinks. However, left-handed DAP DNA was twice as stiff as unmodified L-DNA. Thus, significantly doubly and triply hydrogen bonded segments have very distinct mechanical dynamics at physiological levels of negative supercoiling and tension.

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Biophysical characterization of the association of histones with single-stranded DNA

Abstract: In the cell nucleus histones may spontaneously interact with ssDNA to facilitate their participation in the replication and transcription of chromatin.

Cited by 7 publications

References 61 publications

Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers

Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers

The histone chaperoning pathway: from ribosome to nucleosome

Nanomechanics of negatively supercoiled diaminopurine-substituted DNA

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