COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE

VOLUME XII COLD SPRING HARBOR SYMPOSIA ON ~x.UANTITATIVE BIOLOGY

Founded in 1933 by REGINALD G. HARRIS Director o] the Biological Laboratory 1924 to 1936

The Symposia were organized and managed by Dr. Harris until his death. Their continued use- fulness is a tribute to the soundness o] his vision.

The Symposium volumes are published by the Long Island Biological Association as a part of the work of the Biological Laboratory Cold Spring Harbor, L.I., New York COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XII

Nucleic Acids and Nucleoproteins

THE BIOLOGICAL LABORATORY COLD SPRING HARBOR~ L.I., NEW YORK 1947 COPYRIGHT 1948 BY THE BIOLOGICAL LABORATORY LONG ISLAND BIOLOGICAL ASSOCIATION, INC. All rights reserved. This book may not be reproduced in whole or part, except by reviewers for the public pres% without written perm!~sion from the publisher.

COMPOSED, PRINTED AND BOUND BY GEORGE BANTA PUBLISHING COMPANY, MENASHAp WISCONSIN, U.S.A. FORE WORD

When Nucleic Acids and Nucleoproteins was were concluded with a paper by Schneider on nucleic chosen as the topic of this year's symposium, I was acids in normal and neoplastic tissues. aware that a similar topic had been discussed only Owing to unfortunate circumstances which the a year earlier at the meeting organized by the So- efforts of the Laboratory could not overcome, Belo- ciety for Experimental Biology held at Cambridge zersky and Serra were not able to attend the sym- University. Very few American scientists were able posium. Their papers are included in this volume, to attend the Cambridge meeting, however, so that however. an important segment of current research was not The publication of discussions in this volume is reported. This, together with the fact that research according to the procedure followed for the last two in this field is very active and significant new dis- symposia. Participants were requested to submit coveries had been arrived at since last summer, made manuscripts covering their questions, comments, or the selection of this topic for our symposium an statements if they felt these represented a signifi- appropriate one---particularly since it complements cant contribution. Only the material so received has the subjects of our 9th and 11th symposia (Genes been included in the volume. and Chromosomes and Heredity and Variation in Material presented by Errera and by Ris during Microorganisms) and helps to round out the series the discussions contained new experimental details, of meetings dealing with the mechanism of heredity. and their contributions are published here as sep- For greater ease of reference, the papers in this arate papers. volume are arranged alphabetically according to In the organization of the program for this sym- authors. On the program they were arranged in what posium I was helped by Drs. J. P. Greenstein, A. appeared at the time to be a logical sequence ac- HoUaender, M. McDonald, and A. Mirsky; I wish cording to subject matter. The first group of papers to express to them my sincere appreciation. The to be presented dealt with the chemical aspects of editing was done by Dr. Katherine Brehme Warren. the problem (Greenstein, Carter, and Chalkley; The symposium was held from June 11 to June Schmidt, Cubiles, and Thannhauser; Gulland; 20, 1947. The meetings were attended by about 150 Michaelis). These were followed by Spiegelman and persons. It is my pleasure to acknowledge here a Kamen's paper on the role of nucleoproteins in grant from the Carnegie Corporation, which enabled enzyme formation, and by Taylor, Greenstein, and us to bring scientists from abroad to our meetings. Hollaender's paper on the effect of X-rays on It was with deep regret that we learned of the nucleic acid. Certain aspects of the behavior of death in October of our colleague, John Masson nucleic acids in living cells and tissues were elab- Gulland. He came to us from England to give one of orated in three papers given by Davidson, Thorell, the most significant papers of the Symposium, and and Brachet. This year's program placed consider- his warm personality, as well as the excellence of his able emphasis on the conditions existing in micro- work, made many friends for him in America. Since organisms and on work using microorganisms as his death occurred so soon after our meeting, which experimental material; six papers dealt with research was one of the last that he attended, I feel that it is involving viruses and bacteria (Knight, Hyden, appropriate that we reproduce here a photograph of Cohen, Chargaff, Boivin, and Witkin). Another im- Dr. Gulland and a brief biographical statement pre- portant part of the program was devoted to papers pared by one of his colleagues, and that we dedicate dealing with the nucleus and with chromosomes. this volume to one whose life work and interest were This group included the contributions of Stedman concerned with problems that were discussed at the and Stedman; Mirsky; Pollister and Ris; Schultz; Symposium. and Mazia, Hayashi, and Yudowitch. The sessions M. DEMEREC

Iv] JOHN MASSON GULLAND F.R.S., M.A. (Oxon.), I~.D. (St. Andrews), D.Sc. (Edin.)

JOHN MASSON GULLAND was born in 1898 in Edinburgh, Scotland, son of Professor G. L. Gulland of Edinburgh University. He went to school and University in Edinburgh, but his student days were inter- rupted by the first World War, during which he served as a 2nd Lieutenant in the Royal Engineers from 1917 to 1919. He took his B.Sc. degree in 1921 and later did research work in St. Andrews and Manchester. In 1924 he went to Oxford, where he remained until 1931 when he was appointed Reader in Biochemistry in the Univer- sity of London at the Lister Institute. Five years later he was ap- pointed Sir Jesse Boote Professor of Chemistry in University College, Nottingham. During the second World War he acted as Assistant Director, Chemical Research and Development, Ministry of Supply, from 1943 to 1944; and he had just taken over a new post as Director of Research to the Institute of Brewing when he was killed in a railway accident on 26th October, 1947. He is survived by a widow and two daughters. Gulland's interests ranged over a wide field of Chemistry and Biochemistry, and his early work dealt with alkaloids. Durin~ his stay at the Lister Institute he was engaged on the difficult problem of the pituitary hormones. But it is from his work on the nucleic acids that he will be chiefly remembered. For nearly 20 years he had been engaged in investigating the structure of the nucleic acids and of their constituent nucleofides, and much of our present-day knowl- edge of the chemical constitution of these substances has come from Gulland's laboratory. Gulland was one of the most courteous and charming of men. The invitation to attend the Cold Spring Harbor Symposium on nucleic acids gave him great pleasure, and during his visit to the United States he made many friends who have learned with sorrow of the tragedy which has withdrawn from the field of nucleic acid chemistry one of its foremost investigators. J. N. DAVIDSON Photograph by J. Russell and Sons, London, by courtesy o] the Royal Society LIST OF THOSE ATTENDING OR PARTICIPATING IN THE SYMPOSIUM

.~kBELSON,P. H., Carnegie Institution of Washington, Washington, D.C. .~AMS, MARKH., New York University College of Medicine, New York ALLEN, MARYBELLE, Mallinckrodt Institute of Radiology, St. Louis, Missouri ANDERSON,T. F., University of Pennsylvania, Philadelphia, Pennsylvania ARvocnsw, RACHEl,Biological Laboratory, Cold Spring Harbor, New York BAKER,ArJCE S., , New York BAm~ATT,R. W., Yale University, New Haven, Connecticut BEALE, G. H., Carnegie Institution of Washington, Cold Spring Harbor, New York BELOZE~SKY, A. N., Botanical Institute of Moscow State University, U.S.S.R. BENDICH, AARON,Sloan-Kettering Institute for Cancer Research, New York BERMnN, RUTH, University of Pennsylvania, Philadelphia, Pennsylvania BorvIN, ANDRe, Facult6 de M6decine de Strasbourg, Strasbourg, France BONNER, DAVID, Yale University, New Haven, Connecticut BRACHET,JEAN, University of Brussels, Brussels, Belgium BROWN, GEORGEB., Sloan-Kettering Institute for Cancer Research, New York BRuES, AVSTm M., Argonne National Laboratory, Chicago, Illinois BRYSON, VERNON,Biological Laboratory, Cold Spring Harbor, New York BUCK, JOHN B., National Institute of Health, Bethesda, Maryland BUSCH~:E,WILLIAM H., Johns Hopkins Hospital, Baltimore, Maryland BUSH, MILTONT., Vanderbilt University, Nashville, Tennessee CA~TER, C. E., National Cancer Institute, Bethesda, Maryland CASPARI,ERNST, Wesleyan University, Middletown, Connecticut CHALKLEY,H. W., National Cancer Institute, Bethesda, Maryland C~ARCAFF,E., Columbia University, New York COHEN, SEYMOtmS., University of Pennsylvania, Philadelphia, Pennsylvania COMMONER,BA~RY, Washington University, St. Louis, Missouri COONFIELn, B. R., Brooklyn College, Brooklyn, New York CRIPPEN, MARION,Carnegie Institution of Washington, Cold Spring Harbor, New York CRousE, HELEN V., University of Pennsylvania, Philadelphia, Pennsylvania CRow, JAMESF., Dartmouth College, Hanover, New Hampshire CROWELL,JANE E., Johns Hopkins Hospital, Baltimore, Maryland CUBILES, RICAI~o, Tufts Medical College, Boston, DAXaDSON,1. N., St. Thomas's Hospital Medical School, London, England DEITCI-r,ARLINE D., Columbia University, New York DEME~EC, M., Carnegie Institution of Washington, and Biological Laboratory, Cold Spring Harbor, New York DISCHE, ZACHARL~S,Columbia University, New York DI STEFANO,H., Columbia University, New York DIXON, J., Washington University, St. Louis, Missouri DOYLE, WILLIAML., University of Chicago, Chicago, Illinois EISENBERG,NORMA, Columbia University, New York Eg~ERA, MAtmmE, National Cancer Institute, Bethesda, Maryland, and Fond National de la Recherche Scientifique, University of Brussels, Brussels, Belgium ENGELMAN,MORRIS, Columbia University, New York FANO, UGO, National Bureau of Standards, Washington, D.C. [vii ] viii LIST OF PARTICIPANTS FLhx, MARTIN,Columbia University, New York FOWLER, CATHERINEB., University of Pennsylvania, Philadelphia, Pennsylvania FRICk, HUGO, Biological Laboratory, Cold Spring Harbor, New York FRIEDENWALD,JONAS S., Johns Hopkins Hospital, Baltimore, Maryland FRIEDMAN, FLORENCEL., Washington University, St. Louis, Missouri GALINSKY, IRVING,University of Wisconsin, Madison, Wisconsin GAsxd, G., Universidad de Chile, Santiago, Chile GAULDEN,MARY E., National Institute of Health, Bethesda, Maryland GAY, HELEN, Carnegie Institution of Washington, Cold Spring Harbor, New York GOLDIS,BERNICE, New York University, New York GOODMAN, IRVING,University of Colorado, Boulder, Colorado Gr.AFF, SAMUEL,Columbia University, New York GREE~rSTEIN,J. P., National Cancer Institute, Bethesda, Maryland GRIMSSON, HALLDOR,Princeton University, Princeton, GuLIcx, A., University of Missouri, Columbia, Missouri GtrLLAND,J. M., University College, Nottingham, England HARVEY,ELIZARETH, Yale University, New Haven, Connecticut HAs,:ms, C. P., Haskins Laboratories, New York HAYASHI,T., Columbia University, New York HERSKOWITZ,IRWIN H., Columbia University, New York HoFF~AN, RUTH, Cornell University Medical School, New York HOLLAENDER,A., National Cancer Institute, Bethesda, Maryland HOLTF~, HEINZ, Carlsberg Laboratory, Copenhagen, Denmark HOTCHKISS, R., The Rockefeller Institute for Medical Research, New York HU~3HEs-SCHRADER,SALLY, Columbia University, New York HUSKINS, C. LEONAIU),University of Wisconsin, Madison, Wisconsin HYDtN, H., Karolinska Institutet, Stockholm, Sweden IDDLES, MARCIAK~LMAN, Carnegie Institution of Washington, Cold Spring Harbor, New York JEm~:IN, LILLtAN, New York University Medical School, New York KAMEN, MARTIND., MaUinckrodt Institute of Radiology, St. Louis, Missouri K~ustt, FRED, New York University Medical School, New York KAUFMANN, B. P., Carnegie Institution of Washington, Cold Spring Harbor, New York KAUEMANN, B. W., Johns Hopkins University, Baltimore, Maryland KELNER, ALBERT,Biological Laboratory, Cold Spring Harbor, New York KERSCttNER,JEAN, University of Pennsylvania, Philadelphia, Pennsylvania KLEIN, MORTON,University of Pennsylvania, Philadelphia, Pennsylvania KmGHT, C. A., The Rockefeller Institute for Medical Research, Princeton, New Jersey KODAm, M., University of Rochester, Rochester, New York KRUOELIS,EDITH J., University of Pennsylvania, Philadelphia, Pennsylvania KURNICK, N. B., The Rockefeller Institute for Medical Research, New York LEDERBERG,ESTHER ZIMMER, Yale University, New Haven, Connecticut LEDERtlERG,JOSHUA, Osborn Botanical Laboratory, Yale University, New Haven, Connecticut LEUCHTENBERGER,C., Columbia University, New York L~'-UCHTENRERGER,R., Mount Sinai Hospital, New York LIEB, MARGhR~.T,Barnard College, New York LINDEGREN, CARLC., Washington University, St. Louis, Missouri LtrRtA, S. E., Indiana University, Bloomington, Indiana M~s, WERNER, California Institute of Technology, Pasadena, California MACDOWELL,E. C., Carnegie Institution of Washington, Cold Spring Harbor, New York MACULLA, ESTHER, Yale University, New Haven, Connecticut LIST OF PARTICIPANTS ix [V[AYR,ERNST, American Museum of Natural History, New York MAZIA, DANIEL,University of Missouri, Columbia, Missouri MCCLINTOCK, BARBARA,Carnegie Institution of Washington, Cold Spring Harbor, New York McDONALD, MARGARET,Carnegie Institution of Washington, Cold Spring Harbor, New York MELLORS, R. C., Memorial Hospital, New York ,-'VIICHAELIS,LEONOR, The Rockefeller Institute for Medical Research, New York MILLER, HELENAA., Wellesley College,Wellesley, Massachusetts MIRSKY, A. E., The Rockefeller Institute for Medical Research, New York MOSES, M. J., Columbia University, New York NEWCOMBE, H. B., Carnegie Institution of Washington, Cold Spring Harbor, New York NUSSBAUM,SYI.WA, University of Pennsylvania, Philadelphia, Pennsylvania ORMSBEE, RICHARDA., Sloan-Kettering Institute for Cancer Research, New York PATTERSON, ELIZABETHK., Institute for Cancer Research, Philadelphia, Pennsylvania PETERMANN, MARYL., Sloan-Kettering Institute for Cancer Research, New York POLLISTER, A. W., Columbia University, New York POWERS, E. L., Argonne National Laboratory, Chicago, Illinois PROVASOLX,L., Haskins Laboratories, New York REAUME, S. E., Osborn Botanical Laboratory, Yale University, New Haven, Connecticut REINER, JOHN M., Washington University, St. Louis, Missouri RIDDLE, OSCAR,Plant City, Florida Rts, H., The Rockefeller Institute for Medical Research, New York ROLL, PAULM., Sloan-Kettering Institute for Cancer Research, New York RUDKIN, G~ORGET., Lankenau Hospital, Philadelphia, Pennsylvania RUSSELL, ELIZABETH S., Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine RYAN, FRANCIS, Columbia University, New York SCHMIDT, GERHARD,The Boston Dispensary, Boston, Massachusetts SCHNEIDER, WALTERC., The Rockefeller Institute for Medical Research, l'~ew York SCHRADER,F., Columbia University, New York SCHULTZ, JACK,Lankenau Hospital, Philadelphia, Pennsylvania SnRRA, J. A., University of Coimbra, Coimbra, Portugal SHAPIRO, ARTHUR, 30 Schermerhorn Street, Brooklyn, New York SHULL, A. FRANKLIN,University of Michigan, Ann Arbor, Michigan SONNEBORN,T. M., Indiana University, Bloomington, Indiana SPARRow, A. H., BiologicalLaboratories, Harvard University, Cambridge, Massachusetts SPIEG~LMAN, S., Washington University, St. Louis, Missouri ST. LAWRENCE, PATRICIA, The Rockefeller Institute for Medical Research, New York STEDMAN, EDGAR,University of Edinburgh, Edinburgh, Scotland STEDMAN,ELLEN, University of Edinburgh, Edinburgh, Scotland STEINITZ, LOTTIE M., University of Wisconsin, Madison, Wisconsin STEWART, ROBERTN., Barnard College, New York STOWELL, ROBERTE., Washington University, St. Louis, Missouri STREISINGER, G., Cornell University, Ithaca, New York SWANSTROM,MARVDA, Biological Laboratory, Cold Spring Harbor, New York SWIFT, HEWSON,Columbia University, New York TATU~, E. L., Yale University, New Haven, Connecticut TAYLOR, BABETTE,University of Minnesota, Minneapolis, Minnesota TAYLOR, HARRIETE., Hospital of The Rockefeller Institute for Medical Research, New York TAYLOR, MARTHAJ., Carnegie Institution of Washington, Cold Spring Harbor, New York TEMPLETON, MCCORMICK, Columbia University, New York THANNHAUSER, S. J., Tufts Medical College, Boston, Massachusetts LIST OF PARTICIPANTS THORELL, B., Karolinska Institutet, Stockholm, Sweden TROLL, W~TER, New York University Medical School, New York VAN WAGTENDONK,W. J., Indiana University, Bloomington, Indiana VrLLEE, CLAUDEA., Harvard Medical School, Boston, Massachusetts VISHmAC, WOLF, Hopkins Marine Station, Pacific Grove, California WAELSCH, HEmRICH, Psychiatric Institute and Hospital, New York WARNER, ROBERTC., New York University Medical School, New York WAR~EN, CHARLES0., Commonwealth Fund, New York WARREN, KATHERINE BREHME, New York City WEI, DOROTHYH., Mount Holyoke College, South Hadley, Massachusetts WEIL, ALFREDJ., Lederle Division, Pearl River, New York WEISS~AN, NORMAN, Johns Hopkins University, Baltimore, Maryland WHITE, M. J. D., Carnegie Institution of Washington, Cold Spring Harbor, New York WILSON, KATHERINE,Carnegie Institution of Washington, Cold Spring Harbor, New York WITKIN, E. M., Carnegie Institution of Washington, Cold Spring Harbor, New York WOLLMAN,SEYMOUR H., Sloan-Kettering Institute for Cancer Research, New York WORLEY,LEONAV~ M., Brooklyn College, Brooklyn, New York WYMAN, RUTH, Carnegie Institution of Washington, Cold Spring Harbor, New York YUDOWITCH,KENNETH, University of Missouri, Columbia, Missouri ZAMENHOF, STEPHEN,College of Physicians and Surgeons, Columbia University, New York ZELLE, MAX R., National Institute of Health, Bethesda, Maryland ZITTLE, C. A., Biochemical Research Foundation, Newark, New Jersey CONTENTS

FOREWORD ...... V LIST OF PARTICIPANTS ...... vii BELOZERSKY, A. N'. On the nucleoproteins and polynucleotides of certain bacteria ..... 1 BOIVIN, ANDRe. Directed mutation in colon bacilli, by an inducing principle of desoxyribonucleic nature: its meaning for the general biochemistry of heredity ...... 7 BRACHET, JEAN. The metabolism of nucleic acids during embryonic development 18 CHAROAFF, ERWIN. On the nucleoproteins and nucleic acids of microorganisms ...... 28 COHEN, SEYMOUR S. The synthesis of bacterial viruses in infected cells ..... 35 DAVIDSON, J.N. Some factors influencing the nucleic acid content of cells and tissues .... 50 E~, MAtrRICE. In vitro and in situ action of ionizing radiations on nucleoproteins of the cell nucleus ...... 60 GREENSTEIN, JESSE P., CHARLES E. CARTER and HAROLDW. CHALKLEY. Enzymatic degradation of ribosenucleic and desoxyribosenudeic acids with an addendum on the effect of nucleates on the heat stability of proteins ...... 64 GULr~a~D, JOHN MASSON. The structures of nucleic acids ...... 95 HYDk.N, HOr~GER. The nucleoproteins in virus reproduction ...... 104 KNIOaT, C. A. Nucleoproteins and virus activity ...... 115 MAZIA, DANIEL, TERU HAYASHI and KENNETH YUDOWITCH. Fiber structure in chromosomes lZZ MICHAELIS, L. The nature of the interaction of nucleic acids and nuclei with basic dyestuffs . 131 MmSKY, A.E. Chemical properties of isolated chromosomes ...... 143 POLLISTER, ARTHUR W., and HANS RIS. Nucleoprotein determination in cytological preparations 147 Ris, HaNs. The composition of chromosomes during mitosis and meiosis ...... 158 SCHmIDT, GERHARD, RICARDO CUBILES and S. J. THANNHAUSE~. The action of prostate phosphatase on yeast nucleic acid ...... 161 SCHNEIDER, WALTER C. Nucleic acids in normal and neoplastic tissues ...... 169 SCHULTZ, JACK. The nature of beterochromatin ...... 179 SEm~A, J.A. Composition of chromonemata and matrix and the role of nucleoproteins in mitosis and meiosis ...... 19Z SPIEGELMAN, S., and M. D. KAMEN. Somebasic problems in the relation of nucleic acid turnover to protein synthesis ...... 211 STEDMAN, EDGAR, and ELLEN STEDMAN. The chemical nature and functions of the components of cell nuclei ...... 224 TAYLOR, BABETTE, JESSE P. GREENSTEIN and ALEXANDER HOLLAENDER. The action of X-rays on thymus nucleic acid ...... 237 THORELL, B. The relation of nucleic acids to the formation and differentiation of cellular proteins 247 WlTKrN, EVELYN M. Mutations in Escherichia coli induced by chemical agents ...... 256 INDEX ...... 271 [~] LIST OF PREVIOUS VOLUMES Volume I (1933) Surface Phenomena, 239 pp. Volume II (1934) Aspects of Growth, 284 pp. Volume III (1935) Photochemical Reactions, 359 pp. Volume IV (1936) Excitation Phenomena, 376 pp. Volume V (1937) Internal Secretions, 433 pp. Volume VI (1938) Protein Chemistry, 395 pp. Volume VII (1939) Biological Oxidations, 463 pp. Volume VIII (1940) Permeability and the Nature of Cell Membranes, 285 pp. Volume IX (1941) Genes and Chromosomes: Structure and Organization, 315 pp. Volume X (1942) The Relation of Hormones to Development, 167 pp. Volume XI (1946) Heredity and Variation in Microorganisms, 314 pp.

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