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.
Item is a photocopy.
Number of Image Pages:
2 (478,615 Bytes)
1977-01-17 (January 17, 1977)
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
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.