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I've been reading up about the research concerning the etiological factors behind Alzheimer's and I came across two papers - "Studies on Copper induced stability changes in DNA fragment (GCA ATC TAA TCC CTA): Relevance to Alzheimer’s disease" and "Copper interactions with DNA of chromatin and its role in neurodegenerative disorders." The issue I'm having is that the papers suggest that copper causes the DNA's double helix to unwind in some parts, and it causes it to coil more tightly in others (the fluorescence and circular dichroism research supports the latter).

My question is this: do high concentrations of copper cause DNA to unwind or coil more tightly?

If you could provide any help, I'd be very grateful, as I feel like I'm be missing something obvious.

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  • $\begingroup$ I was able to find your second reference quickly and linked it above, but the first gives more trouble. Can you post a bit more information - bibliographical info or a link? $\endgroup$ Feb 24 at 15:04
  • $\begingroup$ Never mind - found the other link (Young Scientists Journal) online $\endgroup$ Feb 24 at 22:04
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I found your second reference online, which says

Hydrogen bonds are disrupted by the process of partial unwinding which induces structural changes such as loosening of base–base interaction, base tilting and destabilization of the DNA double helix leading to DNA denaturation [17]. The destabilization was due to most probable binding sites in DNA such as Cu2+ to N7 of guanine and N3 of cytosine in line with our present results and with the predictions of Eichhorn and Clark [18], [19].

With this in hand, we can Read The Friendly References. #18 is on PMC and gets the first look - they say "perhaps the structure is"

a structure that looks like it agrees with the previous text

The other references are less helpful for me right now - #17 is a paper from 1971 that's not online and never will be, and #19 talks about histone H1 blocking the copper interaction.

Now what I see here is only unwinding, and is dependent (as proposed) on the presence of G-C base pairs in the sequence. So far from what I've seen, this is based at interactions at around 0.1 mM in in vitro studies, so I feel like it is possible a physiological situation could involve a completely different mechanism.

After writing the above, I found the other paper in Young Scientists Journal - it is quite a remarkable thing to consider. The author is a 12th-grade student from Panama who was doing (among other things) a circular dichroism study and molecular docking with Discovery Studio 3.5. Statistics is lacking and the experiments aren't very well integrated, and the model from the software, which doesn't agree with the image above (it doesn't bind a ring nitrogen in the cytosine), doesn't seem to be tested by the lab data. Despite the sophistication of the software I'm afraid I'm about as skeptical as I was the first time. Still, there is some Ph.D.-level thought there, using some methods that American undergraduates rarely access, conducted by a university in Panama with support from an Indian research institute. Educationally, fascinating.

But I don't see much support for the interpretation in that paper that the DNA coils more tightly. The fluorescence experiment suggests a competition between copper and ethidium bromide, but knowing what actually happens is another story. The CD study ... well, some shifts are identified, one one way and one the other, but I don't see how they prove the DNA is coiling more. But maybe I'm missing something!

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  • $\begingroup$ Thank you, you have cleared this up for me! $\endgroup$
    – AOD
    Feb 25 at 15:21

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