[First posted: 2.03.17/most recent edits & additions: 2.28.17]

See the more recent discussion regarding a more compact DNA structure possibly associated with undifferentiated stem cells at: 'Compact DNA in Stem Cells'

Preamble: this conjecture is an extension of Topics I: Isotopes in the Cell.

Hypothesis: when DNA transitions from its chromatin state to its tightly coiled chromosome state, there occurs a highly energetic structural re-configuration involving roughly a hundred million nucleotides. The kinetic energy of this event creates an opportunity for molecules along the DNA core to explore energetically preferential alternative bonding configurations to those defined by the Watson-Crick structure. The intention here is to consider whether a quantum tunneling effect involving the (O---H-N) and (N-H---N) chain of H-bond linked nucleotides might occur that, subsequently, alters the molecular structure and produces a mutation in the DNA. The hypothesized mutation event might be facilitated by O, H, N isotopes which have either migrated into the DNA core or which have been woven into the molecules during DNA repair processes. While the mutation event may be considered rare, the extreme number of opportunities for such an event to occur within the string of 10^9 active nucleotides in but one of 10^13 cells that reproduce perhaps 10^3 times or more during our lifetime justifies its consideration.

 

 

The conjecture in this section will address the possibility that when DNA is tightly coiled as a chromosome, it may take a slightly modified - more compressed - form than the familiar Watson-Crick structure we see when DNA is uncoiled in its chromatin state. The motivation for this is first to make available the potential energy released by the more compact state, and second, to explore the possible mutations that might result when the envisioned compression/expansion coiling cycle includes isotopic versions of the participating atoms. Our conjecture will focus in on the 2-angstrom gap associated with the h-bond core that runs along the length of the DNA molecule. Consistent with the working hypothesis discussed on the home page, the conjecture is that the alternative structure is a rare occurrence but one available to DNA under specific [hyperfine/tuned] conditions. The possible role such resulting mutations may have with the initiation of cancer is also explored.

One of the important lessons we can borrow from the field of particle physics is a perspective that reminds us that the objects we study should NOT be considered as the sum of the products we see when those objects decay. By example, we see the neutron decay into a 'proton', an 'electron' and an 'anti-neutrino', but the neutron is not to be thought of as being comprised of these three particles. Those labels are properties that pertain only to the neutron's unbound structure. When bound, the neutron is to be considered as being comprised of two 'down quarks' and one 'up quarks', which obtain their own [sense of object] through the interaction of nuclear forces mediated by gluons. This is simple notion is relevant when we consider whether it might apply also to the structure of DNA?

Just to be clear, the images above are three of the highest resolution images we have of DNA. [Ref: Phys. Rev. Let. 102(1) Feb. 2009]. Can we justify the statement that this structure is simply a supercoiled state of the Watson-Crick model? Can we justify the assumption that after such a wild re-organization of energy - as is envisioned to occur during the supercoiling process - the W-C model is still adhered to at each of the roughly 10^8 locations where nucleotide joins nucleotide? Might there be alternative configurations that, under certain conditions, provide a localized potential energy advantage or incentive that can be tapped with minor structural modification? Might we instead consider the W-C model as the opened up decayed state of DNA and consider other possible configurations for its 'bound' (chromosome) state? Or, is such conjecture completely without basis and fruitless to pursue?

We will take the position that while the W-C model might be the most likely structural configuration - the structure we would bet on if we were to roll the dice once, and the structural configuration that might be found in all but a very few locations - that are there less probable configuration states that arise when we roll the dice 10^9 times. And, relevant to the goal of this website, might some of these ‘one-in-a-billion’, ‘drop-it-from-the-data’ type alternatives be responsible for mutation events that lead to cancer.

Let us bring back into view the Watson-Crick model showing the bonding structure of the nucleotides Guanine and Cytosine (below). We want to consider whether the stretched out O---H-N, N-H---N, and N-H---O molecular chains might be reconfigured such that they can provide an energy advantage to the molecules that surround them. Might the 2-angstroms of space that resides along the DNA corridor be reclaimed by the surrounding DNA structure to deliver a more compact >G-C< structure?

We recognize that any such event requires that we overcome the very significant, but classical in origin, Coulomb potential. But a method for overcoming the Coulomb barrier was established decades ago and it can serve as the model for this conjecture - critically, it involves the same N-H---N chain of atom and the protean H-bond structure.

It was established fifty years ago that the proton can change its bonding allegiance and tunnel back and forth between stable H-bond energy states turning N-H---N into N---H-N. This quantum mechanical effect is shown schematically above: the proton in H tunnels from position ‘a’ to position ‘b’ and flips the bonding structure. This structural change was shown to produce tautomeric forms of the nucleotides, which subsequently leads to mismatched base pairs and mutations in DNA. (See: Proton Tunneling in DNA and it Biological Implications. Rev. of Mod. Phys. v.35, no. 3, July 1963.)

We would like to consider slight variations on the above tunneling model - variations that are less likely but energetically feasible as long as we can [coordinate/focus/tap] the free energy of expansion that becomes available in the cytosol when the DNA it envelops is contracted. In most environments rationalizing such events would be impossible. But DNA provides a unique environment - one that has a fine-scaled symmetry like no other. When the thermal energy in the phosphate-sugar backbone is treated as a resource rather than a barrier - a resource that might be tapped when the mirror-image strands establish local coherence - then it opens the door to many quantum mechanical opportunities. Opportunity for occurrence does not necessarily mean that these event do occur, but with 30 trillion cells each with 3 billions base pairs, we've got a sufficiently large pool of events to consider even the statistically rare event.

The first event we will consider starts in a very similar manner as the proton tunneling event shown above, but it results in a dramatic change in final structure.

In this event, the proton begins to tunnel to the right from position ‘a’ to position ‘b' as it did in the previous know event, but we imagine that it possesses a little extra thermal energy - enough so that the proton keeps tunneling right into the nitrogen nucleus. Thermal energy for the event may also be provided if the nitrogen atom in the right is simultaneously kicked towards tunneling proton. Such a tunneling event would convert 14N to 15O resulting in the N-O configuration shown in step D. If the two flanking H-bond locations on the G|C union point can be coerced into similarly configurations, then the compaction of the W-C structure would reclaim the 2-anstom void between the nucleotides and reduce the volume occupied by this region of DNA by as much as 17%. (When the volume available to the cytosol increases, the fluid pressure relaxes and the electromagnetic potential is reduced. This releases potential energy that can help balance the energy needed for tunneling.

An even more likely event might be imagined if we let the 1H hydrogen atom is a 2H deuterium atom, as shown below left, and we look to balance the momentum of the proton moving to the right, with a neutron moving to the left. This also leaves us with an N-O configuration at the nucleotide core. One similar fascinating event is shown in the diagram on the right involving an isotope of nitrogen - this leaves us with an even more symmetrical core structure of O-O.

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[Note: Not shown are the initial spin states of the parent nuclei that can also supply or subtract energy to these events.]

Other interesting possibilities involving other isotopes of N and O will be posted here later this month. A personal favorite involves the release of both an electron and a positron from the collapsed core which subsequently annihilate each other and send two photons blazing out into the cytosol.

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[It may rightly be argued that DNA has many repair mechanisms that can locate and remove any such misbehaving nucleotide. However, per the discussions in topic I, it can also be argued that when those repair molecules open up the tightly woven DNA double helix and exposed it to whatever isotopes might be lurking nearby, the wrong isotope also has a chance of finding its way into the strand and woven back into the DNA molecule upon closure. If nucleotides are grabbed from a storeroom that is filled with aging isotopic nucleotides, the repair process can actually exacerbate the problem (Moe’s theorem).]

[Note that this tunneling events may be seen as related to a family of events involving the inverse of the neutron decay event discussed in topic II: Neutron Decay into a Stable Hydrogen Atom. That event has been calculated to have a branching ratio of ~10^-6. If anyone reading this has the ability to perform a statistical analysis of the likelihood of the tunneling events described in this section, we will be happy to provide our notes on the subject. Of particular interest is the energy associated with the dramatic volume changes associated with these events.]

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This discussion will be expanded in the coming months.
Please return in late spring 2017.

For reference: below is a graphic that illustrates the likely abundance ratio of
specific N-H--O and N-H--N isotopic configurations and their expected count per cell. See also the discusion in Topic I: Isotopes in the Cell
.


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