Nuclear Mechanics and Genome Regulation


Book Description

In recent years new discoveries have made this an exciting and important field of research. This exhaustive volume presents comprehensive chapters and detailed background information for researchers working with in the field of nuclear mechanics and genome regulation. Both classic and state-of-the-art methods readily adaptable and designed to last the test of time Relevant to clinicians and scientists working in a wide range of fields




Introduction to Nuclear Mechanics and Genome Regulation


Book Description

Introduction to Nuclear Mechanics and Genome Regulation provides a detailed discussion of the biophysical principles underlying nuclear organization and their role in determining tissue function, cell differentiation and homeostasis, and disease expression and management. Applied case studies and full cover images support concept illustration across a diverse range of chapters covering physico-chemical constraints in DNA, 3D organization of chromosomes and functional gene clusters, spatial dimensions of DNA transcription, replication, damage and repair, and more. With its practical approach and foundational focus, this book will be an invaluable reference for students, researchers and clinicians looking to understand this area of cutting-edge study. Contains applied case studies and full color images that support concept illustration Features a diverse range of chapters that cover the fundamentals of nuclear mechanics and genome regulation, including physico-chemical constraints in DNA Introduces advanced biophysical methods, bio-imaging methods, and new molecular biology tools for studying nuclear structures




Intermediate Filament Proteins


Book Description

Intermediate Filament Proteins, the latest volume in the Methods in Enzymology series covers all the intermediate filaments in vertebrates and invertebrates, providing a unique understanding of the multiple different tissue-specific intermediate filaments. This volume also covers the latest methods that are currently being used to study intermediate filament protein function and dynamics. It will be an important companion for any experimentalist interesting in studying this protein family in their cell or organism model system.




Nuclear Structure and Gene Expression


Book Description

Nuclear Structure and Gene Expression assimilates the contributions of genome organization and of the components of the nuclear matrix to the control of DNA and RNA synthesis. Nuclear domains which accommodate DNA replication and gene expression are considered in relation to short-term developmental and homeostatic requirements as well as to long-term commitments to phenotypic gene expression in differentiated cells. Consideration is given to the involvement of nuclear structure in gene localization as well as to the targeting and concentration of transcription factors. Aberrations in nuclear architecture associated with and potentially functionally related to pathologies are evaluated. Tumor cells are described from the perspective of the striking modifications in both the composition and organization of nuclear components. Nuclear Structure and Gene Expression presents concepts as well as experimental approaches, which define functionality of nuclear morphology. * Mechanisms of interaction between nuclear structure and genes * Gene expression regulation by elements of the nuclear matrix * How nuclear structure exerts a regulatory effect on other aspects of cell function/physiology




A Coarse-Grained Molecular Dynamics Model of the Mammalian Nuclear Envelope


Book Description

The cell nucleus houses most of the genetic material in eukaryotic cells and is the site of many fundamental genome regulatory processes including cell division, gene expression, differentiation, and aging. The regulation of architecture of the nuclear envelope (NE) is essential for smooth operation of these processes. There is currently no physics-based model, theoretical or computational, which accounts for all significant interactions of subnuclear components in a common framework, leaving much of NE mechanics unexplored and poorly understood. We present a coarse-grained molecular dynamics model of the mammalian NE of unprecedented detail. A three-step protocol is shown to generate a coarse-grained nuclear envelope (CGNE) with experimentally consistent structure. The CGNE features a monolayer model of the nuclear membranes and a dynamically-linked meshwork model of the underlying nuclear lamina. Peripheral chromatin, which supports the meshwork from underneath and also interlaces with it, is modeled as a chain of mesoscale domains. The methodologies for in silico mechanical testing of the CGNE and extraction of metrics of NE viscoelasticity from the simulation data are described. Parameters are being tuned towards achieving experimental consistency of these viscoelastic properties. A revised CGNE model is planned to be published elsewhere in the near future.




CELL GEOMETRY.


Book Description




Cancer Biology and the Nuclear Envelope


Book Description

"Nuclear envelope (NE) defects have been linked to cancer biology since the mid-1800s, but it was not until the last few years that we have begun to understand these historical links and to realize that there are myriad ways that the NE impacts on tumorigenesis. The NE is a complex double membrane system that encloses the genome while providing structural support through the intermediate filament lamin polymer and regulating protein/ mRNA trafficking and signaling between the nucleus and cytoplasm via the nuclear pore complexes (NPCs). These functions already provide some mechanisms for NE influences on cancer biology but work in the past few years has elucidated many others. Lamins and many recently identified NE transmembrane proteins (NETs) have been now shown to function in DNA repair, regulation of cell cycle and signaling, apoptosis, cell migration in metastasis and nuclear architecture and morphology. This volume presents a comprehensive overview of the wide range of functions recently identified for NE proteins and their relevance in cancer biology, providing molecular mechanisms and evidence of their value as prognostic and diagnostic markers and suggesting new avenues for the treatment of cancer. Indeed some of these recent links are already yielding promising therapies, such as the current clinical trial of selective inhibitors of the nuclear export factor exportin in certain types of leukemia, melanoma and kidney cancer."




Nuclear Pore Complexes in Genome Organization, Function and Maintenance


Book Description

The three-dimensional organization of the DNA inside the eukaryotic cell nucleus has emerged a critical regulator of genome integrity and function. Increasing evidence indicates that nuclear pore complexes (NPCs), the large protein channels that connect the nucleus to the cytoplasm, play a critical role in the establishment and maintenance of chromatin organization and in the regulation of gene activity. These findings, which oppose the traditional view of NPCs as channels with only one: the facilitation of nucleocytoplasmic molecule exchange, have completely transformed our understanding of these structures. This book describes our current knowledge of the role of NPCs in genome organization and gene expression regulation. It starts by providing an overview of the different compartments and structures of the nucleus and how they contribute to organizing the genome, then moves to examine the direct roles of NPCs and their components in gene expression regulation in different organisms, and ends by describing the function of nuclear pores in the infection and genome integration of HIV, in DNA repair and telomere maintenance, and in the regulation of chromosome segregation and mitosis. This book provides an intellectual backdrop for anyone interested in understanding how the gatekeepers of the nucleus contribute to safeguarding the integrity and function of the eukaryotic genome.




Nuclear Architecture and Dynamics


Book Description

Nuclear Architecture and Dynamics provides a definitive resource for (bio)physicists and molecular and cellular biologists whose research involves an understanding of the organization of the genome and the mechanisms of its proper reading, maintenance, and replication by the cell. This book brings together the biochemical and physical characteristics of genome organization, providing a relevant framework in which to interpret the control of gene expression and cell differentiation. It includes work from a group of international experts, including biologists, physicists, mathematicians, and bioinformaticians who have come together for a comprehensive presentation of the current developments in the nuclear dynamics and architecture field. The book provides the uninitiated with an entry point to a highly dynamic, but complex issue, and the expert with an opportunity to have a fresh look at the viewpoints advocated by researchers from different disciplines. Highlights the link between the (bio)chemistry and the (bio)physics of chromatin Deciphers the complex interplay between numerous biochemical factors at task in the nucleus and the physical state of chromatin Provides a collective view of the field by a large, diverse group of authors with both physics and biology backgrounds