Author: Lisa Yu
Publisher:
ISBN: 9780494581254
Category :
Languages : en
Pages : 352
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Book Description
Proper progression through the cell cycle is critical for cell growth and survival. Disruption of cell cycle progression can lead to cell cycle arrest and cell death. In addition, uncontrolled cell cycle progression can lead to cancer. Cells have evolved complex mechanisms to regulate each phase of the cell cycle to ensure proper cell cycle progression. In the presence of cellular stress, cells will respond promptly to arrest the cell cycle and allow repair. In order to study this complex process, it is important to identify the complete complement of proteins involved. I took two large-scale approaches to study the cell cycle. First, I down-regulated the majority of essential genes in Saccharomyces cerevisiae, and determined how depletion of individual gene product affected progression through the cell cycle. I determined that over 65% of essential genes I tested are most important at a specific cell cycle phase. In addition, I found that two genes, Smc4 and Cse1, have novel roles in S-phase of the cell cycle. In the second approach, I discovered two anti-proliferative compounds. Both compounds caused cell cycle delay in G1 phase of the cell cycle. Chemical genetic screens in yeast allowed me to determine the pathways most sensitive to each of these two compounds. By studying the response of cells to these compounds, I confirmed that compound 13 causes mitochondrial dysfunction in cells and compound 15 causes nuclear DNA damage. Furthermore, I found that both compounds are toxic in mammalian cells and that the responses that they elicit in mammalian cells are similar to those observed in yeast cells.
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Book Description
Author: Jennifer L. Paulson
Publisher:
ISBN:
Category :
Languages : en
Pages : 292
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Book Description
Protein phosphorylation is a ubiquitous regulatory mechanism for cellular signal propagation, and the complexity of signaling networks presents a challenge to protein kinase substrate identification. Chemical genetic control of kinase function provides a handle for kinase pathway analysis. Here, we apply this approach to three kinases that function in a signaling network that regulates exit from mitosis in the budding yeast, Saccharomyces cerevisiae. These include the mitogen-activating protein kinase, Cdc15, the nuclear Dbf2-related kinase, Dbf2, and the Polo-like kinase, Cdc5. Each kinase was successfully engineered for selective chemical inhibition in vivo. We found that monospecific pharmacological inhibition of Cdc5 delays anaphase nucleus migration into the bud, revealing a novel Cdc5 function. Additionally, chemical genetic, bioinformatic, and yeast proteomic tools were combined for Cdc5 substrate identification. Systematically chosen candidate Cdc5 substrates were examined for loss of phosphorylation upon cellular Cdc5 inhibition. The identified Cdc5 targets include Spc72, a spindle pole body (SPB) component and microtubule anchor required for nuclear positioning. Spc72 binds Cdc5 in a cell cycle specific manner, and in vivo Cdc5 inhibition prevents mitotic Spc72 phosphorylation. Studies in vitro demonstrate direct Spc72 phosphorylation by Cdc5. Finally, we expanded our knowledge of Cdc5 function at the SPB by examining SPB-localized proteins for presence in a Cdc5 complex. In summary, a chemical genetic approach was used to inhibit three protein kinases from diverse families, which led to a greater understanding of Cdc5 cellular function.
Author: Vincenzo E.A. Russo
Publisher: Springer Science & Business Media
ISBN: 3642770436
Category : Science
Languages : en
Pages : 633
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Book Description
As a result of the molecular genetic analysis of development similar mechanisms for the regulation of gene expression are found in a wide range of organisms. In "Development - the Molecular Genetic Approach" these common mechanisms as well as the specific events leading to a differentiated cell are described. Particular items treated are, for example, how asymmetry is achieved, how cell size is determined, how cell division is controlled, how cell lineage influences development, how cells know their position, and how cells communicate during development.
Author: Ralph G. Wilkins
Publisher: Royal Society of Chemistry
ISBN: 178262760X
Category : Science
Languages : en
Pages : 281
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Book Description
This book features humans (a lot), other mammals (a good deal) and, occasionally, other animals to illustrate principles.
Author: Scott Allen Hoose
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Cell replication and division are central to the proliferation of life, and have implications for normal growth and development as well as disease state. Assembly of a complete picture of the systems which control this process requires identification of individual genetic components, but the identity and complete sequence of events that trigger initiation of cell division, at a point called START in yeast, remain unknown. Here, we evaluated panels of non-essential single gene deletion strains and tested the effects of FDA-approved drugs on cell-cycle progression, using flow cytometry to detect altered DNA content. Previous studies relied mainly on cell size changes to systematically identify genes required for the timely completion of START. This analysis revealed that most gene deletions that altered cell-cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell-cycle control mechanisms. We found that cystathionine-beta-synthase (CBS) advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function which does not require that activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, it is generally not known whether the compounds tested alter the timing of particular cell-cycle transitions. Our approach revealed strong cell-cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell-cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation. Our studies not only transform our view of START, but also expand the repertoire of genetic and chemical means to modulate the eukaryotic cell cycle.
Author: Benzecri
Publisher: CRC Press
ISBN: 058536303X
Category : Mathematics
Languages : en
Pages : 684
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Book Description
This practical reference/text presents a complete introduction to the practice of data analysis - clarifying the geometrical language used, explaining the formulae, reviewing linear algebra and multidimensional Euclidean geometry, and including proofs of results. It is intended as either a self-study guide for professionals involved in experimental
Author: C. Nicolini
Publisher: Springer Science & Business Media
ISBN: 940115550X
Category : Science
Languages : en
Pages : 340
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Book Description
Proceedings of the NATO Advanced Study Institute on Genome Structure and Function, held in Marciana Marina, Elba, Italy, 13-23 June 1996
Author: David M. Prescott
Publisher: Elsevier
ISBN: 0323147798
Category : Science
Languages : en
Pages : 508
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Book Description
Cell Biology, A Comprehensive Treatise, Volume 2: The Structure and Replication of Genetic Material is mainly about the structure and replication of genetic material in both the nucleus and cytoplasmic organelles. This volume is part of the first four volumes that establish a firm foundation regarding issues of cell structure and function. These issues include cell reproduction, differentiation, and cell-to-cell interactions. This book is divided into nine chapters. Each chapter deals extensively with chromosomes – its physical, genetic, and chemical structures. In addition, this book explains the replication of chromosomes in terms of the cell cycle, as well as their coding capacity. It also discusses the functional organization (structure and levels) of the chromosomes. The concluding chapters present the DNA replication molecular principles and enzymatic machinery. Furthermore, this book explains DNA repair and its relationship to various biological endpoints. The authors of this book reasonably explain and emphasize already established facts and concepts in terms that are relatively easy to understand. Undergraduate and graduate students, teachers, researchers, scientists, and others interested or in need of information regarding cell biology will find this book of great use.
Author: Lester Goldstein
Publisher:
ISBN:
Category : Cytology
Languages : en
Pages : 516
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Book Description
