Table Of ContentNucleic Acids in Chemistry and Biology
3rd Edition
Nucleic Acids in Chemistry
and Biology
3rd Edition
Edited by
G. Michael Blackburn
Centre for Chemical Biology, Department of Chemistry, University of Sheffield, Sheffield, UK
Michael J. Gait
Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
David Loakes
Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
David M. Williams
Centre for Chemical Biology, Department of Chemistry, University of Sheffield, Sheffield, UK
ISBN-10: 0-85404-654-2
ISBN-13: 978-0-85404-654-6
A catalogue record for this book is available from the British Library
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Foreword
It was just 62 years ago that we finally learned that DNA was the genetic material – the master blueprint
of life. Since then, the nucleic acids DNA and RNA have been studied in exquisite detail and both their
chemical and biochemical properties are firmly established. Indeed, the double helical structure of DNA
has become an icon of our time appearing widely not only in the scientific literature, but also in the popu-
lar press and most recently as jewelry. A thorough knowledge of nucleic acids and their properties is now
a key ingredient in the education of both biologists and chemists. Ten years ago the second edition of
“Blackburn & Gait” was published and seemed sufficiently comprehensive that only small additions
would be needed if it were ever to be rewritten. Its popularity is attested to by its now being out of print –
it has also inevitably become out of date. Much has changed in the last 10 years and a new edition is now
both necessary and most welcome.
One major discovery within the biological arena has been the phenomenon of RNA interference, which
was not even mentioned in the last edition, and yet at this time several companies have been formed to cap-
italize on it and at least one product is heading into clinical trials. We also now know that short micro-
RNAs play key roles in development and are probably of ubiquitous importance in controlling gene
expression. These and other small RNAs are likely to play a much more critical and subtle role in the lives
of cells than we might ever have imagined. I find this personally very satisfying, since, when we discov-
ered split genes and RNA splicing in 1977, the introns were almost immediately labeled “junk”. It now
seems that at least some of these intronic sequences play positive roles in controlling gene expression and
their involvement in other processes may still await discovery. Studies of small RNAs in eukaryotes are
proceeding quickly and I eagerly await the results from similar studies in bacteria and archaea. It seems
likely that great discoveries lie ahead although new methods may be required to make them. The develop-
ment of such methods will be greatly facilitated by a thorough knowledge of the chemistry and biology of
nucleic acids – the subject of this book.
Among the great technical achievements of the last 10 years have been several breakthroughs in the
scale of DNA sequencing. First came the complete sequence of a simple bacterium, Haemophilus influen-
zae, quickly followed by that of the first archaea, Methanocaldococcus jannaschii.A key feature of these
projects was the use whole-genome shotgun sequencing pioneered by Craig Venter. These “small” genomes
were soon followed by draft sequences for a number of eukaryotic genomes including, of course, the draft
human genome sequence announced in 2003 and coinciding with the 50th anniversary of the determina-
tion of the structure of DNA by Jim Watson and Francis Crick. With more recent advances in sequencing
technologies that use highly parallel methodology, one machine can now generate enough data for a small
bacterial genome in a few hours, at a quite reasonable price. We can anticipate an even more massive
influx of new data in the next few years. The accumulation of sequence data far exceeds our experimental
capacity to probe it. Fortunately, bioinformatics stands ready to help and with appropriate experimental
input, should allow us to make sense of the terabases (1012) of DNA sequence data that will soon be pres-
ent in GenBank. In parallel with these improvements in DNA sequence determination, techniques for
DNA synthesis have progressed rapidly. It has now become so simple and inexpensive that many labora-
tories find it more expedient to have the genes of interest synthesized rather than to clone them. Among
other things, this allows the introduction of desirable codons tailored to the expression system to be used.
vi Foreword
All of this new work serves to highlight the intertwining of chemistry and biology that has taken place over
the last 50 years. Those wishing to understand this interrelationship and appreciate the excitement cur-
rently present in the field can do no better than browse the many excellent chapters in this third edition of
Nucleic Acids in Chemistry and Biology.
Richard J. Roberts
Preface
The first edition of Nucleic Acids in Chemistry and Biology in 1990 met the pressing need for a single vol-
ume that integrated the chemistry and biology of nucleic acids in an introductory yet authoritative text.
That book was so very well received that in 1996 we produced the second edition, which was completely
revised and rewritten by very much the same team of international experts.
Ten years on we have responded to the still growing need for this book with a fully revised and updated
third edition. Two irresistible pressures have driven this activity. First, the expansion in the chemistry and
biology of nucleic acids continues unabated. The human and numerous lesser genomes have been fully
sequenced since we presented the second edition and there has been a veritable explosion in the chemistry
and biology of RNA. Many exciting crystal and NMR structures of nucleic acids and their protein com-
plexes, including the ribosome, have been published. Changes of such magnitude have inevitably made
significant parts of the 1996 text out of date. We have addressed these issues by expansion of the appro-
priate sections of the book and also by new authorship. Second, the second edition sold out several years
ago. Indeed second-hand copies are occasionally available on the web at a handsome premium!
In planning this third edition, we first expanded the team of editors to include two younger colleagues,
David Loakes and David Williams. We then changed publishing house to move under the roof of the Royal
Society of Chemistry. For a variety of reasons it has been necessary to make changes to the team of prin-
cipal authors and we thank especially Stephanie Allen, Martin Egli, Julie Fisher, Andy Flavell, Ihtshamul
Haq, Charles Laughton, Ben Luisi, Anna Marie Pyle, Elliott Stollar, and Nick Williams for their essential
and scholarly contributions. With the active support of the Royal Society of Chemistry and its commis-
sioning and production teams, we have made significant changes in the style of presentation of this new
edition. It now has a bibliography of primary and secondary sources that are referenced throughout the
text. While we have maintained a number of multi-colour illustrations in addition to our standard two-
colour format, we have abandoned the use of stereo-pair illustrations and the end-of-section summaries.
These changes have created space for some expansion – but not enough for our needs: the third edition has
grown substantially compared to its predecessor! This has enabled the authors to introduce a great deal of
new material. In doing so, we have retained the essential core of chemistry and biology that has made this
book so effective as a teaching resource at every level of study and an initiation into the molecular basics
of nucleic acids. A selection of figures that may have value for course teachers are available electronically
at the following website: http://www.rsc.org/books/nucleicacids
Above all, we have endeavoured to maintain the quality of the earlier editions, both of which have been
widely appreciated for their easy readability, simplicity of exposition, clarity of illustration, and uniformity
of style. That has underpinned our efforts to deliver a new edition that once again fulfils the needs of students
and new research workers, primarily those having a chemical and biochemical background who seek to
understand this great subject at a molecular level. Indeed, we know that Nucleic Acids in Chemistry and
viii Preface
Biology has become the course-book of choice in universities across three continents. At the same time, from
many favourable comments on editions 1 and 2 we know that this book has also reached out to more senior
scientists across many disciplines.
G Michael Blackburn
Michael J Gait
David Loakes
David M Williams
Acknowledgements
Two Mikes and two Davids are extremely grateful for the efforts of all who have supported the production
of this book. Our unqualified thanks are given above all to our 10 expert and understanding co-authors,
whose contributions have made possible this third edition. We express our sincere appreciation of their
patience, tolerance, and enthusiastic diligence during the numerous revision processes required for the
production of the completed work.
We are also very grateful to very many colleagues and fellow scientists who have provided us with valu-
able comments on the first two editions of the text and especially those who have read portions of the new
edition. They include Jason Betley, Chris Calladine, Rick Cosstick, Steve Fodor, Dan Gewirth, Alec
Jeffreys, David Lilley, Kiyoshi Nagai, Barbara Nawrot, Frank Seela, Jean Thomas, Andrew Travers, and
David Wilson. We are once again indebted to Joachim Engels forupdating and expanding the glossary and
to Rich Roberts for writing the forward for this edition.
The technical production of this book has been enabled by many skilled individuals. We particularly
appreciate the efforts of all the staff involved in the Royal Society of Chemistry for their enthusiasm,
patience, and highly professional production of the completed work. We and our co-authors gratefully
acknowledge the efforts of Fred Anston, John Brazier, Pat Mellor, Sabuj Pattanayek, and Wenke Zhang
who have facilitated the completion of figures and text in various chapters. In particular we are greatly
indebted to Annette Lenton who has redrawn, recoloured, or reworked very many of the figures in order to
achieve a homogeneous standard and style. We thank Venki Ramakrishnan for providing original graphics
for the cover of the third edition of the book and Richard Dickerson, Stephen Lippard, and Dinshaw Patel
for illustrative figures.
Last but not least, we have enjoyed receiving a large number of positive and helpful comments from
readers of the first two editions. We have endeavoured to incorporate all constructive criticisms into the
new edition. In particular we thank colleagues around the world whose strong support provided much
motivation for the creation of this third edition.
Despite all our careful work, it is inevitable that there will be some errors and we accept full responsi-
bility for them. Finally, we look forward to your advice, comments, and suggestions for future revisions.
