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Author: Beth A. Rasala
Publisher:
ISBN: 9780549423874
Category :
Languages : en
Pages : 241
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Book Description
My thesis is focused upon molecularly defining the mechanism of early steps in metazoan nuclear pore assembly. Nuclear pore complexes (NPCs) are large proteinaceous structures that span the nuclear envelope and act as gated aqueous channels to regulate the transport of macromolecules between the nucleus and cytoplasm. In metazoans, the massive NPCs disassemble into soluble subunits at the beginning of mitosis and then somehow reassemble following chromosome segregation; a process that is coordinated with membrane recruitment and fusion. The mechanism and order of NPC assembly is poorly understood. In Chapter 1, I show that ELYS co-purifies with the Nup107-160 complex, the largest subunit of the NPC, in Xenopus egg and human cell extracts. Indeed, I demonstrate that ELYS is a dual nucleoporin/kinetochore protein required for nuclear pore assembly and proper cell division. In Chapter 2, I focus on defining the early steps in nuclear pore assembly, including the mechanism for ELYS as the pore 'targeting' protein. In Chapter 3, I collaborated with Dr. Corinne Ramos on a study to order pore assembly with respect to inner and outer nuclear membrane fusion. Taken the data from chapters 1-3 together, I suggest a model in which NPC assembly is initiated on AT-rich chromatin through an interaction with the C-terminus of ELYS. The data also show the chromatin binding of ELYS precedes and is required for the binding of the Nup107-160 complex. Chromatin-bound ELYS and the Nup107-160 complex then recruit integral pore membrane proteins POM121- and NDC1-containing membrane vesicles. Membrane vesicle fusion takes place to form patches of continuous double nuclear membranes. Oligomerization of ELYS/Nup107-160/POM121 then acts to promote fusion between the inner and outer nuclear membranes to form a diffusion channel. Finally, the remaining soluble pore subunits are recruited to assemble the mature, functional nuclear pore. Finally, Appendix B presents data on the Xenopus binding partners of the C-terminus of Nup160, a member of the Nup107-160 complex, which was derived from mass spectrometry analyses. This data led to the discovery that vertebrate centrin 2 localizes to NPCs and functions in mRNA and protein export, as described in Chapter 4.
Author: Beth A. Rasala
Publisher:
ISBN: 9780549423874
Category :
Languages : en
Pages : 241
Get Book Here
Book Description
My thesis is focused upon molecularly defining the mechanism of early steps in metazoan nuclear pore assembly. Nuclear pore complexes (NPCs) are large proteinaceous structures that span the nuclear envelope and act as gated aqueous channels to regulate the transport of macromolecules between the nucleus and cytoplasm. In metazoans, the massive NPCs disassemble into soluble subunits at the beginning of mitosis and then somehow reassemble following chromosome segregation; a process that is coordinated with membrane recruitment and fusion. The mechanism and order of NPC assembly is poorly understood. In Chapter 1, I show that ELYS co-purifies with the Nup107-160 complex, the largest subunit of the NPC, in Xenopus egg and human cell extracts. Indeed, I demonstrate that ELYS is a dual nucleoporin/kinetochore protein required for nuclear pore assembly and proper cell division. In Chapter 2, I focus on defining the early steps in nuclear pore assembly, including the mechanism for ELYS as the pore 'targeting' protein. In Chapter 3, I collaborated with Dr. Corinne Ramos on a study to order pore assembly with respect to inner and outer nuclear membrane fusion. Taken the data from chapters 1-3 together, I suggest a model in which NPC assembly is initiated on AT-rich chromatin through an interaction with the C-terminus of ELYS. The data also show the chromatin binding of ELYS precedes and is required for the binding of the Nup107-160 complex. Chromatin-bound ELYS and the Nup107-160 complex then recruit integral pore membrane proteins POM121- and NDC1-containing membrane vesicles. Membrane vesicle fusion takes place to form patches of continuous double nuclear membranes. Oligomerization of ELYS/Nup107-160/POM121 then acts to promote fusion between the inner and outer nuclear membranes to form a diffusion channel. Finally, the remaining soluble pore subunits are recruited to assemble the mature, functional nuclear pore. Finally, Appendix B presents data on the Xenopus binding partners of the C-terminus of Nup160, a member of the Nup107-160 complex, which was derived from mass spectrometry analyses. This data led to the discovery that vertebrate centrin 2 localizes to NPCs and functions in mRNA and protein export, as described in Chapter 4.
Author: Valerie Anne Delmar
Publisher:
ISBN:
Category :
Languages : en
Pages : 122
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Book Description
The nucleus is the defining structure of eukaryotic cells. The nuclear envelope acts as a barrier between nucleus and cytoplasm. Nuclear pore complexes perforating the envelope control all traffic into and out of the nucleus, and thus act to regulate transcription, translation, and other essential cellular processes. During mitosis, the nuclear envelope from flies to mammals disassembles into its component parts, with the nuclear pore breaking into multiple subunits. The pore then reassembles in a step-wise process as the nuclear envelope reforms in late anaphase. The major focus of this thesis has been to better understand the assembly and function of the nuclear pore. It has resulted in three published papers and one paper in preparation. First, I participated, with postdoc Dr. Corine Lau, in a study of the novel vertebrate transmembrane nucleoporin, Ndc1. I resolved the topology of yeast Ndc1p and identified conserved amino acids to target for future functional studies (Chapter 1). In a second study, I participated in a collaboration with the laboratory of Dr. Pamela Silver at Harvard Medical School in identifying a new role for the vertebrate nuclear pore in the regulation of transcription. We found that in vertebrates, specific chromosomal regions move to the nuclear pore complexes during transcriptional activation (Chapter 2). Key work next centered on the mechanism of action of importin beta in negatively regulating nuclear membrane fusion and pore assembly. (The small GTPase, Ran, positively regulates both these processes.) A major unanswered question has been, which specific steps in nuclear pore assembly are regulated by importin beta or RanGTP. I determined, using Xenopus constructs, that importin beta is an authentic regulator of nuclear pore assembly and that, contrary to previously published results, Ran reverses this negative regulation (Chapter 3). Finally, a fourth study, done with Dr. Corine Lau, established that the distant importin beta relative, transportin, also negatively regulates nuclear membrane and pore assembly (Chapter 4). I showed that both transportin and importin beta act early to control the initial step of pore assembly: the binding of the pore-targeting protein ELYS to chromatin, which sets in motion the specific targeting of nuclear pores to the nuclear surface.
Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0
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Book Description
Author: Reiner Peters
Publisher: Springer Science & Business Media
ISBN: 3642715656
Category : Science
Languages : en
Pages : 296
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Book Description
Author: American Bar Association. House of Delegates
Publisher: American Bar Association
ISBN: 9781590318737
Category : Law
Languages : en
Pages : 216
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Book Description
The Model Rules of Professional Conduct provides an up-to-date resource for information on legal ethics. Federal, state and local courts in all jurisdictions look to the Rules for guidance in solving lawyer malpractice cases, disciplinary actions, disqualification issues, sanctions questions and much more. In this volume, black-letter Rules of Professional Conduct are followed by numbered Comments that explain each Rule's purpose and provide suggestions for its practical application. The Rules will help you identify proper conduct in a variety of given situations, review those instances where discretionary action is possible, and define the nature of the relationship between you and your clients, colleagues and the courts.
Author: Irwin M. Arias
Publisher: John Wiley & Sons
ISBN: 1119436826
Category : Medical
Languages : en
Pages : 1156
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Book Description
Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.
Author: Sue Shackleton
Publisher: Humana
ISBN: 9781493935284
Category : Science
Languages : en
Pages : 0
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Book Description
This volume provides a wide range of protocols used in studying the nuclear envelope, with special attention to the experimental adjustments that may be required to successfully investigate this complex organelle in cells from various organisms. The Nuclear Envelope: Methods and Protocols is divided into five sections: Part I – Nuclear Envelope Isolation; Part II – Nuclear Envelope Protein Interactions, Localization, and Dynamics; Part III – Nuclear Envelope Interactions with the Cytoskeleton; Part IV – Nuclear Envelope-Chromatin Interactions; and Part V – Nucleo-Cytoplasmic Transport. Many of the modifications discussed in this book have only been circulated within laboratories that have conducted research in this field for many years. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting edge and thorough, The Nuclear Envelope: Methods and Protocols is a timely resource for researchers who have joined this dynamic and rapidly growing field.
Author: Christophe Lavelle
Publisher: Academic Press
ISBN: 012803503X
Category : Science
Languages : en
Pages : 620
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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
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309142393
Category : Law
Languages : en
Pages : 348
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Book Description
Scores of talented and dedicated people serve the forensic science community, performing vitally important work. However, they are often constrained by lack of adequate resources, sound policies, and national support. It is clear that change and advancements, both systematic and scientific, are needed in a number of forensic science disciplines to ensure the reliability of work, establish enforceable standards, and promote best practices with consistent application. Strengthening Forensic Science in the United States: A Path Forward provides a detailed plan for addressing these needs and suggests the creation of a new government entity, the National Institute of Forensic Science, to establish and enforce standards within the forensic science community. The benefits of improving and regulating the forensic science disciplines are clear: assisting law enforcement officials, enhancing homeland security, and reducing the risk of wrongful conviction and exoneration. Strengthening Forensic Science in the United States gives a full account of what is needed to advance the forensic science disciplines, including upgrading of systems and organizational structures, better training, widespread adoption of uniform and enforceable best practices, and mandatory certification and accreditation programs. While this book provides an essential call-to-action for congress and policy makers, it also serves as a vital tool for law enforcement agencies, criminal prosecutors and attorneys, and forensic science educators.
Author: Weidong Yang
Publisher: Springer
ISBN: 3319773097
Category : Science
Languages : en
Pages : 277
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Book Description
Dysfunction of nuclear-cytoplasmic transport systems has been associated with many human diseases. Thus, understanding of how functional this transport system maintains, or through dysfunction fails to maintain remains the core question in cell biology. In eukaryotic cells, the nuclear envelope (NE) separates the genetic transcription in the nucleus from the translational machinery in the cytoplasm. Thousands of nuclear pore complexes (NPCs) embedded on the NE selectively mediate the bidirectional trafficking of macromolecules such as RNAs and proteins between these two cellular compartments. In this book, the authors integrate recent progress on the structure of NPC and the mechanism of nuclear-cytoplasmic transport system in vitro and in vivo.
