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The Double Non-Helix Ken Biegeleisen, M.D., Ph.D. |
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W-C twisted structure in |
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DNA structure in living systems: non-helical! |
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The Plain and Simple Truth Fact: the circular single strands of a double-stranded circular plasmid or viral chromosome can be separated, intact, without breaking either one open. Furthermore, the separated strands can be re-annealed to give the native duplex structure with all its properties restored:
Neither of these things would be possible if circular DNA had the Watson-Crick twisted structure:
The fact that scientists choose to ignore this does not make it any less true. The historical record confirms that in the days of Galileo, scientists - and even the Pope himself - knew that the earth was not the center of the universe. They deliberately chose to ignore it. We thus learn that prejudice reigns supreme today, just as it did centuries ago.
The Heart of the Problem If you want to understand anything, follow the money. The reason scientists have erred about DNA structure for over 50 years is that there's simply too much money in genetic engineering. It doesn't matter what the structure of the DNA is, as it's flung into one side of the pharmaceutical money-making vat, as long as dollars keep pouring out the other side. Thus, the vast majority of researches in DNA structure involve only primary structure, i.e., the DNA sequence, because that's where the money is. Meanwhile, the few scientists who attempt to investigate intranuclear DNA-protein structure are hamstrung by insisting that every such study begin with the Watson-Crick "double helix". All such studies are doomed to failure in advance, because there's no way to anastomose the negative charges of a "double helix" with the positive charges on nuclear proteins.
History The moment John Cairns discovered that the E. coli chromosome was circular, the Watson-Crick structure suddenly became an unlikely one for living systems . That was way back in 1963, only 10 years after the publication of the world-famous Nature article on the "double-helix" structure. Aside from DNA polymerase, none of the enzymes of DNA replication were known then, and the huge conceptual problems involved in the replication of a circular chromosome were not addressed, but merely ignored. Consider that the E. coli chromosome contains 4 million base pairs, which, if twisted up into the Watson-Crick helix, would consist of 400,000 helical turns. During cell division, each and every one of those turns must be unwound and re-wound, sometimes in as little as 20 minutes. That means that the chromosome, in log phase, spins at 20,000 rpm continuously! That's 20 times faster than an electric drill! How did the molecular biology "establishment" of 1963 react to this absurd presumption? Instead of considering the possibility that DNA, in living systems, where it is inevitably complexed with highly-conserved basic protein, might have a different structure than DNA in synthetic, artifactually-deproteinized crystals, they chose, rather deliberately, to all-but-forbid discussion of any structure other than the "double-helix". Why? Because, in the spiritual realm, DNA had become - in only 10 short years - a quasi-religious icon, like a "sacred cow", not to be touched. In the financial realm, the Watson-Crick structure had also provoked a torrential flow of research dollars, and any serious criticism might have interfered with the flow of the only "truth" that really matters to most people these days - money. So what did they do? They proceeded to confabulate excuses to explain the alleged lightening-fast unwinding and re-winding of DNA during cell replication. The first such excuse was the "swivel", a totally hypothetical mechanism, something like an automobile universal joint, which provided a theoretical point about which DNA could spin at 20,000 rpm. I do not object to the proposal of a "swivel", but to do so while forbidding the discussion of non-helical structures - which require no unwinding in the first place - is misleading, to say the least. It’s true that our knowledge of DNA replication has advanced astonishingly since then, and that the enzymes topoisomerase and gyrase theoretically allow unwinding of DNA, as the DNA replication fork advances along the chromosome. But the incredibly complex and minutely-coordinated processes of DNA replication take place within a flattened-out; that is, non-helical region of activity in the replicating fork, whereas topoisomerase/gyrase acts outside this region. The roles of the enzymes within the fork are apparently well-characterized, and complicated in the extreme; described in Lehninger's textbook as “elegant enzymatic choreography”. However, the supposed “winding and unwinding” events, outside the replicating fork, are a much more murky affair. There is no demonstrated temporal relationship between the well-documented “choreography” of the enzymes within the replicating fork, and the murky activities of the topoisomerases and gyrases without. Most topoisomerase and gyrase research is based upon in vitro studies, where the native structure of DNA is destroyed; a fact most scientists inexplicably choose to overlook: As soon as you remove DNA from its natural protein environment, it’s going to wind itself up into a helix, and everything you discover subsequently is at risk of being laboratory artifact. As for in vivo studies, the literature is so confusing, and the publications so mutually inconsistent, that it’s hard to find a well-enough established fact to merit a critical analysis. The typical so-called "two-domain" experiment involves either activation of conditional enzyme mutants, or administration of enzyme poisons, neither of which necessarily even stops DNA replication, but may merely slow it down. The products generated may or may not be supercoiled in various senses, according to 2-dimensional electrophoresis gels which are exceedingly difficult to interpret. Virtually any result reported in one lab has been contradicted by a different result elsewhere. In the presence of such uncertainty, it would be foolish to draw too many conclusions from this line of research. Even if topoisomerase/gyrase do what they are claimed to do in vitro, isn’t it possible that in the living cell their true roles may be in other processes, such as DNA repair? See The Double Non-Helix, Part I & Part II The facts about DNA structure have now been assembled into a 2-disk set of PowerPoint presentations. Part I, which runs 3 hours in length, describes the history of DNA topology. Part II, which runs over an hour, describes the structure of the protamine-DNA complex in minute detail, and shows the incontrovertible logic from which it was derived. From these presentations you will learn the following:
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You do not need to purchase the CDs to learn about this subject. Much of their content is on the Not-A-Helix web site. |
