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:~/
rthur M. Sackler
C O L L O Q U I A
OF THE NATIONAL ACADEMY OF SCIENCES
Self-Perpetuating Structural States in
Biology, Disease, and Genetics
Eclitecl by Susan Linguist and Steve Henikoff
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1
Ill
Cover photograph: Ribbon diagram of the protein structural interface
associated with the disease amyloidogenic protein transthyretin. The
side chains of naturally occurring mutations, which influence the age
and severity of disease onset, are shown in white. These mutations
alter the energy landscape of the partially unfolded protein. This in
turn can either exacerbate or prevent disease. Image courtesy of
Ted Foss. See article by Hammarstrom et al. on pages 16427-16432.
This work is reprinted from the Proceedings of the National Academy
of Sciences of the United States of America, vol. 99, suppl. 4, pp.
16377-16506, December 10, 2002, and includes articles from the
Arthur M. Sackler Colloquium on Self-Perpetuating Structural States
in Biology, Disease, and Genetics, held at the National Academy of
Sciences in Washington, DC, March 22-24, 2002. The articles
appearing in these pages were contributed by speakers at the
colloquium and were anonymously reviewed, but they have not been
independently reviewed by the Academy. Any opinions, findings,
conclusions, or recommendations expressed in this work are those of
the authors and do not necessarily reflect the views of the National
Academy of Sciences.
The National Academy of Sciences is a private, nonprofit,
self-perpetuating society of distinguished scholars engaged in
scientific and engineering research, dedicated to the furtherance of
science and technology and to their use for the general welfare. Upon
the authority of the charter granted to it by the U.S. Congress in
1863, the Academy has a mandate that requires it to advise the
Federal Government on scientific and technical matters.
ISBN: 309-08445-8.
(3 Copyright by the National Academy of Sciences, USA
All rights reserved. Published 2002
Printed in the United States of America
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<_Arthur M. Sack/er
_ C O L L O Q U I A
~~
OF THE NATIONAL ACADEMY OF SCIENCES
Self-Perpetuating Structural
States in Biology, Disease,
and Genetics
National Academy of Sciences
Washington, D.C.
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Arthur M. Sackler, M.D.
1 91 3-1 987
Born in Brooklyn, New York, Arthur M. Sackler was edu-
cated in the arts, sciences, and humanities at New York
University. These interests remained the focus of his life, as he
became widely known as a scientist, art collector, and philan-
thropist, endowing institutions of learning and culture through-
out the world.
He felt that his fundamental role was as a doctor, a vocation
he decided upon at the age of four. After completing his
internship and service as house physician at Lincoln Hospital in
New York City, he became a resident in psychiatry at Creed-
moor State Hospital. There, in the 1940s, he started research
that resulted in more than 150 papers in neuroendocrinology,
psychiatry, and experimental medicine. He considered his
scientific research in the metabolic basis of schizophrenia his
most significant contribution to science and served as editor of the Journal of Clinical and
Experimental Psychobiology from 1950 to 1962. In 1960 he started publication of Medical Tribune,
a weekly medical newspaper that reached over one million readers in 20 countries. He
established the Laboratories for Therapeutic Research in 1938, a facility in New York for basic
research that he directed until 1983.
As a generous benefactor to the causes of medicine and basic science, Arthur Sackler built
and contributed to a wide range of scientific institutions: the Sackler School of Medicine
established in 1972 at Tel Aviv University, Tel Aviv, Israel; the Sackler Institute of Graduate
Biomedical Science at New York University, founded in 1980; the Arthur M. Sackler Science
Center dedicated in 1985 at Clark University, Worcester, Massachusetts; and the Sackler School
of Graduate Biomedical Sciences, established in 1980, and the Arthur M. Sackler Center for
Health Communications, established in 1986, both at Tufts University, Boston, Massachusetts.
His pre-eminence in the art world is already legendary. According to his wife Jillian, one of
his favorite relaxations was to visit museums and art galleries and pick out great pieces others
had overlooked. His interest in art is reflected in his philanthropy; he endowed galleries at the
Metropolitan Museum of Art and Princeton University, a museum at Harvard University, and
the Arthur M. Sackler Gallery of Asian Art in Washington, DC. True to his oft-stated
determination to create bridges between peoples, he offered to build a teaching museum in
China, which Jillian made possible after his death, and in 1993 opened the Arthur M. Sackler
Museum of Art and Archaeology at Peking University in Beijing.
In a world that often sees science and art as two separate cultures, Arthur Sackler saw them
as inextricably related. In a speech given at the State University of New York at Stony Brook,
Some rejections on the arts, sciences and humanities, a year before his death, he observed:
"Communication is, for me, theprimum movens of all culture. In the arts. . . I find the emotional
component most moving. In science, it is the intellectual content. Both are deeply interlinked
in the humanities." The Arthur M. Sackler Colloquia at the National Academy of Sciences pay
tribute to this faith in communication as the prime mover of knowledge and culture.
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PNAS
Proceedings of the National Academy of Sciences
of the United States of America
Contents
Papers from the Arthur M. Sackler Colloquium of the National
Academy of Sciences
INTRODUCTION
16377 Self-perpetuating structural states in biology, disease,
and genetics
Susan L. Lindquist and Steven Henikoff
COLLOQUIUM PAPERS
16378 Transmission of prions
C. Weissmann, M. Enari, P.-C. Klohn, D. Rossi,
and E. Flechsig
16384 Conservation of a portion of the S. cerevisiae Ure2p
prion domain that interacts with the full-length protein
Herman K. Edskes and Reed B. Wickner
16392 Interactions among prions and prion "strains" in yeast
Michael E. Bradley, Herman K. Edskes, Joo Y. Hong,
Reed B. Wickner, and Susan W. Liebman
16400 Identification of benzothiazoles as potential
polyglutamine aggregation inhibitors of Huntington's
disease by using an automated filter retardation assay
Volker Heiser, Sabine Engemann, Wolfgang Brocker,
Ilona Dunkel, Annett Boeddrich, Stephanie Waelter,
Eddi Nordhoff, Rudi Lurz, Nancy Schugardt, Susanne
Rautenberg, Christian Herhaus, Gerhard Barnickel,
Henning Bottcher, Hans Lehrach, and Erich E. Wanker
16407 Chaperoning brain degeneration
Nancy M. Bonini
16412 Molecular chaperones as modulators of polyglutamine
protein aggregation and toxicity
Hideki Sakahira, Peter Breuer, Manajit K. Hayer-Hartl,
and F. Ulrich Hartl
16419 Studies of the aggregation of mutant proteins in vitro
provide insights into the genetics of amyloid diseases
Fabrizio Chiti, Martino Calamai, Niccolo Taddei,
Massimo Stefani, Giampietro Ramponi,
and Christopher M. Dobson
16427 Sequence-dependent denaturation energetics: A major
determinant in amyloid disease diversity
Per Hammarstrom, Xin Jiang, Amy R. Hurshman,
Evan T. Powers, and Jeffe~y W. Kelly
16433 The insulation of genes from external enhancers and
silencing chromatin
Bonnie Burgess-Beusse, Catherine Farrell, Miklos Gaszner,
Michael Litt, Vesco Mutskov, Felix Recillas-Targa,
Melanie Simpson, Adam West, and Ga~y Felsenfeld
16438 Histone H3 Iysine 4 methylation is mediated by Set1
and promotes maintenance of active chromatin
states in fission yeast
Ken-ichi Noma and Shiv I. S. Grewal
16446 Changes in the middle region of Sup35 profoundly alter
the nature of epigenetic inheritance for the yeast
prion lPSI+]
Jia-Jia Liu, Neal Sondheimer, and Susan L. Lindquist
16454 Heritable chromatin structure: Mapping "memory" in
histones H3 and H4
Christine M. Smith, Zara W. Haimberger, Catherine 0.
Johnson, Alex J. Wolf, Philip R. Gafken, Zhongli Zhang,
Mark R. Parthun, and Daniel E. Gottschling
16462 Does heterochromatin protein 1 always follow code?
Yuhong Li, Dawn A. Kirschmann, and Lori L. Wallrath
16470 Self-perpetuating epigenetic pill switches in bacteria
Aaron Hernday, Margareta Krabbe, Bruce Braaten,
and David Low
16477 Histone H3 variants specify modes of
chromatin assembly
Kami Ahmad and Steven Henikoff
16485 Induction and maintenance of nonsymmetrical DNA
methylation in Neurospora
Eric U. Selker, Michael Freitag, GregoIy 0. Kothe,
Brian S. Margolin, Michael R. Rountree, C. David Allis,
and Hisashi Tamaru
16491 Locus-specific control of asymmetric and CpNpG
methylation by the DRM and CMT3
methyltransferase genes
Xiaofeng Cao and Steven E. Jacobsen
16499 RNA-directed DNA methylation in Arabidopsis
Werner Aufsatz, M. Florian Mette, Johannes van der Winden,
Antonius J. M. Matzke, and Marjori Matzke
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