Nuclear Structure and Function Research Group

DESCRIPTION

By the end of the nineteenth century, biologists understood that the gross anatomy of an organism directly underpinned its life style. One hundred years later, we can carry this understanding all the way to the molecular level, relating the geometry of individual biomolecules to the way they carry out their functions. At an intermediate level, we expect different parts of the cell to perform different functions. The architecture of the mitochondrion is so exquisitely interlinked with energy production, and the cytoskeleton with cell support and movement, that discussing function without a knowledge of structure is impossible. We would expect the same to apply to the nucleus, with clearly-defined regions carrying out specific functions; however, the nuclear interior is generally depicted in our textbooks as a featureless tangle of chromatin fibres. Of course, it is not like that, and this book is based on the belief that an understanding of nuclear function goes hand in hand with an understanding of nuclear architecture. Most examples are chosen from the animal world, simply because less is known about plant nuclei; they often have a medical interest, because I teach medical students as well as other biologists.

The structure of the book is as follows:
Chapter 1 serves two main purposes - to summarize material that most students have met before (eg the structure of DNA and RNA), and to introduce some general problems and solutions.
Chapter 2 covers the structures of the nucleus and its subcompartments, the chromatin fibre, and chromosomes.
Chapters 3-5 describe the vital nuclear processes of replication, transcription, and the repair of damage in DNA.
Chapters 6-7 go on to discuss the control of these processes.
Chapter 8 covers meiosis and recombination.

PREFACE

By the end of the nineteenth century, biologists understood that the gross anatomy of an organism directly underpinned its life style. One hundred years later, we can carry this understanding all the way to the molecular level, relating the geometry of individual biomolecules to the way they carry out their functions. At an intermediate level, we expect different parts of the cell to perform different functions. The architecture of the mitochondrion is so exquisitely interlinked with energy production, and the cytoskeleton with cell support and movement, that discussing function without a knowledge of structure is impossible. We would expect the same to apply to the nucleus, with clearly defined regions carrying out specific functions; however, the nuclear interior is generally depicted in our textbooks as a featureless tangle of chromatin fibers. Of course, it is not like that, and this book is based on the belief that an understanding of nuclear function goes hand in hand with an understanding of nuclear architecture. Most examples are chosen from the animal world, simply because less is known about plant nuclei.
This book also promotes the idea that the key players in the nucleus - the active polymerases - are attached to discrete structures within nuclei. Polymerases were initially purified and analyzed using approaches that destroyed those structures, so traditional models for polymerase action attach little significance to nuclear architecture. I describe briefly the traditional models, before discussing variants where architecture plays a crucial role. This book, then, is addressed to students entering the field, and to those working in it who wish to put their results in this newer structural context. I leave it to the reader to decide whether this alternative view provides a better approximation to the truth than the traditional one.

AUTHOR BIO

Peter Cook received his doctorate at The University of Oxford. As the E.P. Abraham Professor of Cell Biology at the University of Oxford and a Professorial Fellow of Lincoln College, he teaches students of biology and medicine.
His research interests include the analysis of the way chromosome structure influences gene activity. He is currently combining the techniques of molecular biology with those of high-resolution imaging to map active sites of replication and transcription within three-dimensional nuclear space. These studies have led to the surprising finding that active genes are not spread diffusely throughout the nucleus; rather, they are concentrated in discrete sites or 'factories' where the appropriate molecular machines (ie the DNA and RNA polymerases) are concentrated.

 

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