Lack of Z-DNA Conformation in Mitomycin-Modified Polynucleotides Having Inverted Circular Dichroism

Poly(dG-dC)· poly(dG-dC) and Micrococcus lysodeikticus DNA were modified by exposure to reductively activated mitomycin C, an antitumor antibiotic. The resulting covalent drug-polynucleotide complexes displayed varying degrees of CD inversions, which are strikingly similar to the inverted spectrum observed with Z-DNA. The following criteria have been used to establish, however, that the inverted CD pattern seen in mitomycin C-polynucleotide complexes does not reflect a Z-DNA conformation. (i) The ethanol-induced transition of poly(dG-dC)· poly(dG-dC) from B to Z conformation is not facilitated but rather is inhibited by mitomycin C modification. This may be due to the presence of crosslinks. (ii) Radioimmunoassay indicated no competition for Z-DNA-specific antibody by any of the mitomycin C-modified polynucleotides. (iii) 31P NMR of the complexes yielded a single relatively narrow resonance, which is inconsistent with the dinucleotide repeat characteristic of Z-DNA. Alternative explanations for the inverted CD pattern include a drug-induced left-handed but non-Z conformational change or the superposition of an induced CD onto the CD of B-DNA due to drug-base electronic interactions. These results illustrate the need for caution in interpreting CD changes alone as an indication of Z-DNA conformation

Competition between B-Z and B-L transitions in a single DNA molecule: Computational studies

Under negative torsion, DNA adopts left-handed helical forms, such as Z-DNA and L-DNA. Using the random copolymer model developed for a wormlike chain, we represent a single DNA molecule with structural heterogeneity as a helical chain consisting of monomers which can be characterized by different helical senses and pitches. By Monte Carlo simulation, where we take into account bending and twist fluctuations explicitly, we study sequence dependence of B-Z transitions under torsional stress and tension focusing on the interaction with B-L transitions. We consider core sequences, (GC)(n) repeats or (TG)(n) repeats, which can interconvert between the right-handed B form and the left-handed Z form, imbedded in a random sequence, which can convert to left-handed L form with different (tension dependent) helical pitch. We show that Z-DNA formation from the (GC)(n) sequence is always supported by unwinding torsional stress but Z-DNA formation from the (TG)(n) sequence, which are more costly to convert but numerous, can be strongly influenced by the quenched disorder in the surrounding random sequence.National Research Foundation NRF-2012 R1A1A3013044 NRF-2014R1A1A2055681NRF-2012R1A1A2021736IBS-R023-D1NRF-2015R1A2A2A01005916Chemistr

Dynamic phase transition in the conversion of B-DNA to Z-DNA

The long time dynamics of the conformational transition from B-DNA to Z-DNA is shown to undergo a dynamic phase transition. We obtained the dynamic phase diagram for the stability of the front separating B and Z. The instability in this front results in two split fronts moving with different velocities. Hence, depending on the system parameters a denatured state may develop dynamically eventhough it is thermodynamically forbidden. This resolves the current controversies on the transition mechanism of the B-DNA to Z-DNA.Comment: 5 pages, 4 figures. New version with correction of typos, new references, minor modifications in Fig 2, 3. To appear in EP

The Buoyant Behavior of Viral and Bacterial DNA in Alkaline CsCl

In equilibrium density gradient centrifugation, the banding polymer species is electrically neutral. The banding species for a negative polyelectrolyte with a polyanion P_(n)^(-z)n (where n is the degree of polymerization, and z the titration charge per monomer unit) in a CsCl salt gradient is CS_(zn)P_n. If the ion P_(n)^(-z)n is itself a weak acid, it may be titrated to the state P_(n)^(-(Zn+y)) by CsOH; the banding species is then Cs_(zn+y)P_n. Because of the large mass and high effective "density" of a Cs^+ ion, it is to be expected that the buoyant density in a CsCl gradient of a polymer acid will be increased by such a partial alkaline titration with CsOH. This expectation has been confirmed for polyglutamic acid (where z = 0 at low pH). The guanine and thymine monomer units of DNA are weak acids. The present communication is concerned with the increase in buoyant density of DNA in alkaline CsCl solutions. It is well known that the guanine and thymine protons are more readily titrated in denatured DNA than in native DNA. We find that the buoyant density of denatured DNA and of single strand ϕX-174 DNA gradually increases as the pH of the solution is increased beyond pH 9.8. The density of native DNA is not affected until a critical pH > 11 is reached, where the DNA abruptly denatures and increases in density. Similar increases in buoyant density have been observed independently by Baldwin and Shooter in their studies of 5BU[overbar]-substituted DNA's in alkaline solutions

Z-DNA forming regions in the human genome

Z-DNA is the left-handed helical structure of the usually right-handed B-DNA double helix structure. Z-DNA conformations have been found to cause mutagenesis and genetic instability [1]. In this study, human genome sequences potentially forming Z-DNA regions (ZDRs) were extracted and analysed for functional implications

Structure of d(TGCGCA)(2) and a comparison with other DNA Hexamers

The X-ray crystal structure of d(TGCGCA)(2) has been determined at 120 K to a resolution of 1.3 Angstrom. Hexamer duplexes, in the Z-DNA conformation, pack in an arrangement similar to the 'pure spermine form' [Egli et al. (1991). Biochemistry, 30, 11388-11402] but with significantly different cell dimensions. The phosphate backbone exists in two equally populated discrete conformations at one nucleotide step, around phosphate 11. The structure contains two ordered cobalt hexammine molecules which have roles in stabilization of both the Z-DNA conformation of the duplex and in crystal packing. A comparison of d(TGCGCA)(2) with other Z-DNA hexamer structures available in the Nucleic Acid Database illustrates the elusive nature of crystal packing. A review of the interactions with the metal cations Na+, Mg2+ and Co3+ reveals a relatively small proportion of phosphate binding and that close contacts between metal ions are common. A prediction of the water structure is compared with the observed pattern in the reported structure

Models of DNA denaturation dynamics: universal properties

We briefly review some of the models used to describe DNA denaturation dynamics, focusing on the value of the dynamical exponent $z$, which governs the scaling of the characteristic time $\tau\sim L^z$ as a function of the sequence length $L$. The models contain different degrees of simplifications, in particular sometimes they do not include a description for helical entanglement: we discuss how this aspect influences the value of $z$, which ranges from $z=0$ to $z \approx 3.3$. Connections with experiments are also mentioned