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The Francis Crick Papers

Letter from Francis Crick to Aaron Klug pdf (478,615 Bytes) transcript of pdf
Letter from Francis Crick to Aaron Klug
Crick expressed reservations about the evidence used by his two co-authors in support of their idea that chromatids, the one-half of a chromosome that splits off from the other half during cell division, were organized in a hierarchy of helices: the chromatid is a folded and coiled super-solenoid (a long, regular, hollow cylindrical structure), also called the unit fiber, which in turn is formed by a coiled solenoid of smaller diameter, which in turn is formed by coiling the string of nucleosomes, bead-like complexes of DNA and protein.
See Leth Bak, Jesper Zeuthen, and Crick, "Higher-Order Structure of Human Mitotic Chromosomes," Proceedings of the National Academy of Sciences, vol. 74 (April 1977), pp. 1595-99.
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2 (478,615 Bytes)
1977-01-17 (January 17, 1977)
Crick, Francis
Klug, Aaron
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
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From Molecular Biology to Neurobiology, 1976-2004
Metadata Record Letter from Aaron Klug to Francis Crick (March 11, 1977) pdf (541,331 Bytes) transcript of pdf
Metadata Record Letter from Aaron Klug to Francis Crick (January 27, 1977) pdf (260,618 Bytes) transcript of pdf
Metadata Record Higher-Order Structure of Human Mitotic Chromosomes (April 1977) pdf (664,021 Bytes) ocr (21,675 Bytes)
Box Number: 23
Folder Number: PP/CRI/D/2/18
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Document Type:
Letters (correspondence)
Physical Condition:
Series: Correspondence
SubSeries: Individual Correspondents
Folder: Correspondence with Aaron Klug
January 17, 1977
Dear Aaron,
I enclose a copy of a short paper by Bak, Zeuthen and myself which I have just sent off to PNAS. I have not been entirely successful in my efforts to get Bak to do what I consider necessary to make his results solid (though he was kind enough to send me about 1000 of his photographs!) so that I have some reservations about the reliability of it all, but it was clear that we whould either have to leave it all till August or send it off now more or less as it is. If he comes to London you may be able to get a firmer impression of him. My worries concern the reliability of measuring something of diameter 0.4 um with the light microscope, the variability of this figure both along a fiber and between fibers, the evidence for "doubleness" and its interpretation, the effects of different salts, methods of fixation, staining, etc. (I enclose xerox copies of some of my recent letters to him which deal with these and other points.) I have managed to remove most of the nonsense from the section on 'The Final Level of Folding' but have quite failed to convince them that their double helix is almost certainly wrong. Anyway, let me know what you think of it. I have reluctantly come to the conclusion that if the general idea of a 7 x 6 x 40 x 5 hierarchy is correct, the telling evidence will come from other people rather than from Bak and Zeuthen.
Worcel was here. He gave quite a good seminar. Again, you will hear it all in London. The new idea is that the nucleosomes/unit turn of the solenoid is a function of the exact "200" b.p. repeat. They assume that for 190 b.p. the nucleofilament is straight. For 200 b.p. there are about 8 nucleosomes/turn, for 220 b.p. about 3 -- the relationship is a continuous one. For figures less than 190 the solenoid is right-handed rather than left-handed. You will see how this is derived though he expressed it in a cumbersome way. I imagine the approximate formula is
n = (N - 190)/95
It assumes (roughly speaking) that the curvature of the DNA is constant and that 'extra' DNA, above or below 190 (which represents exactly 2 turns of DNA) is used to form the extra 'turns' (between dyads) needed for the supersolenoid. He explained it all in terms of H1 interactions but they were not qualified.
As far as I know there is no evidence for any such relationship (for instance, the exact diameter of a supersolenoid should vary with the "200" b.p. repeat and be a little smaller for erythrocytes than for liver, for example) but I suspect there is some relationship of this sort. It's possible it might even lead, if combined with kinking, to a supersolenoid. It's clearly going to be another case of pseudo-symmetry. Perhaps it's time we started to think about it again.
Yours ever,
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