11 March 1977 Br. F. X. C. Crick, FRS, Salk Institute, t Office Box 1808, saa Diego, California B2ll2, U.S.A. Dear Francis, Thank you for yo f am sorry I have not to surface after my v Firstly, about your note on Len's work. I have discussed ths various points you raised in detail with Leu and he fa going to do the controls you mention. He immediately on his return statement that the removal of his resu1.t. In any entromere. Indeed I found d raised the other buffers. On the w adn't beeu attached to it, it would probably e at the back at the Royal Soc Bak and Zeuthen's work to that The meetings themselves went quite well. all around. Zachau had sented some o Dr. F'. I;. C. Crick, FRS -2- I1 March 1977 results ou reconstltutkoir *&ab I13 and H4 on1 . This leads to particles of about 75-80 2 diameter (compared with 95 w for semisomes) and they seem able to organise 120-130 base pairs on their owu, indeed rather like the results claimed by Felsenfsld in another type af experiment. I saw FelsenfePPd briefly in Boatom who told me they had yet another paper in press on this subject. Varshavsky turned out to be very impressive, although in his talk he showed so many gel patterns, siosZly unlaballed, that it became very dkfficult to follow. However, he cane to the Lab. the following week with Engelhardt and gave a much clearer seminar. Be spoke mostly about three dfffereut types of ~lonomess and the sub-nucleosomal fractions. There is a wealth of beta91 and, rather than swamarise it all, I am sending you a copy of his nanuscript. I must say I don't know what csnclusiona one caar draw from it but there are some rather interesting associatfons of nan-histone protehe with som0 of ths fractions. One generalisation is that the smaller fragments of DNA seen to be aasocfated with about one hiotoue each. Varehavsky speaks very good English and was altogether verg impsesoPse. I am glad we invited him but I rather fear that he may rua into trouble in the future since he is rather outspoken about conditions there mdihis own situation (Having blurted quite a Lot out ov0r lunch here as though Ire were impelled to cis 80) be able to cone to tine Cold Spring Harbor meetilng bsaauso both Georgiev and Nirzabekov will be going. I am writfng 8 letter of thanzks to Engeltaardt in which I will end by saying I hope to see Varafaavsky at CSB. he then etsksd us not to repeat anythfng in c8se the word got back.) 4 e thinks Be may not Roger gave an excellent talk. What he show was there was no phasing, but the mast striking result came out as a By-product. lie urns a combination of exonuclease 3 (which only r8moves ople strand of double stranded DNA) plus 81 (which only acts on single strand&. DNA) to trim monomers and dimers down to a llrnit in Beparate experiments. The dimer does not of DNA betwe ~S-~O. I regard trdls result The monomer bad sharp eautifully and this AS the COX.€t?Xbl. clwioxn is that there fs a variable length cL.--.-.-.-.I^--.-*".._Ic---- "-I-^ -- -- I. ri;e-coadursiv would in any C868 be impossible, although in %he dk8CU8SioU PrPoph Out that 'ithi9 eXpl&fZld Why phaising ) raised the question 8s to whether the phasing could be restored in the next higher level of structure, say at the dodacaaser level. I suppose one could invent other explanaeiona such as the two free ends of a UNA on the djimer corning close together and therefore inhibiting trimming, but I prefer Roger's simple explanation. The rest of tho meeting want very well I thought, %any of the people had already been to two earlier meetings on ths subject of DRA sequences (ths Harden Canfarenee last September and one in Switzerland in January) but, eo moat of the audience, a Pot of Cbs resulW were new and very wall presented. Ilogness' work in part?lcular was spectacular but 1 asstune you bow all about that. There wtw a lot of discussion as to whether beads are present on the DHA during transcription a~d Franke was adamant on the basis of e.m. evidence that they ape not. Laird was guarded. The situation wasn't wade any clearer by Joel Gottssfeld's paper. He spoke very clearly and 1 must saw I reallv can't see what 2s wrong with the experiments now that he * . Dr. F. H. C. Crick, FRS -3- 1 Marc . 1977 experiment seems to be that he can convert the 14s particle to the 11s particle in the 8ame tube by treatment with RNase. this up for Nucleic Acids Reeearch and f wil a copy so that, even if it all. turns out to rang, It won*-& be obvious at this stage. He Is writing *e sure that you get I think the hit of the meeting was Ashburner who substituted for Brian Clarke who was ill. Ashburner went into a very detailed analysis of tha zest white region of drosophila and pointed out that there are strong reasons to dispute the one gene-one band hypothesis. out that tests for saturation would be difficult or invalid (since the phenomenon didn't obey poisson statistics), tk orge Lefebl-0 had shown that many mutations werev without ~BCFOZSC (adding that he could practically hear you callirrg that the largest bands were probably too large ~f9Fi'j~f~R ,- that they were unlikely to contasln s~edal bands. 1 must say that I hope there isn't a straw man involked here. He gave the impression that the one gene-one band hypothesis was so sloppy as not to be worthwhile, but surely one can nodify it to one band-one a&& of genes operating together et sim. However I must say that 1 f Hopess' results there doesn't s0em to be a lot of the genes he has looked at which are now genes and heat shock genes* He points henotype, that there was at least one baud wh4ch produced three e -a; -_ GKc ; Worcel gave a good talk and errssenti you had already alerted me to. It is rather clever but I am beginning to think that clever conjectures? by bright people, wfthout any supporting evidence, are rapidly becoming the bane of the chromatin field. What Worcel didn't talk about was the parallel between bacteria and drosophila but I tried to make this clear in some rernark;sr f made. At the EM30 Workshop, most of the atuff was structural, and the only new thing was a model by Pardon and R4chards who presented a %hick by 110 2 in diameter with the DNA right on the outside, turns, about 30 Iz rt. It may not be such nonsense as some the audience though gcause people are fixed on the idea of a spherical bead. The Workshop itself was not a great success because there were so many wantfng to speak that I simply decided to allow theB 10 to 15 minutes each. by Keller (I. enclose 8 copy of his abstract). uce Ponder aleo described his work. This was the first time I had followed it in detail. I found ft amazing that he got t Bme pattern of eco.Rl b whichever cut of the original mnomer material he took, i.et the 240-170 bme pair region or 170-200. Since one gets discrete bands fn the eco R1 digestion, on0 seems forced to couclude that there is a correlation between the alternative positions of the eco R1 site and the alternative lengths of the microceccal nuclease digestion products. t the neutron and scattering data in solution. This was of' about 58 There was a good thing ! ! I I i I ~ i 1 Dr. Ii. c. Crick, PES -4- 11 GIarch 187%' Thats a11 for now. Sydney and. Max have told me about your plans and although we haven't talked about it the ~ord seems to have got around o I will. write 680~1 about progress with the crystals. We now have some evidence that the packing I descril~oct to you in ray letters 0% September and October is correct but we don't know what the units are that are being packed, efther nmLessomes or semi-nucleosomes. 9 hope to prepare an internal memo on the subject and will send you a copy. Irr the meantine, we are trying to grow bigger ~rystktls tu measure the dsnslLy, of whfch we only have limits. Yours ever, Eleca. 3