Download or read book Dissecting the Functions of Atr in Replication Fork Stability written by Theonie Anastassiadis and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome maintenance is required for cellular viability, and failure to preserve genomic integrity is associated with an increased risk of diseases, such as cancer. To ensure genomic stability, cells have checkpoints that control cell cycle progression in the event of DNA damage or incomplete DNA replication. The DNA replication checkpoint is regulated by the ATR-CHK1 pathway that stabilizes stalled replication forks and prevents their collapse into DNA double-strand breaks (DSBs). Two distinct models have been proposed to explain how ATR stabilizes stalled forks: 1) through local modulation of fork remodelers, such as SMARCAL1 inhibition, and 2) through inhibition of CDK-dependent pathways, such as inhibition of the AURKA-PLK1 pathway, which prevent cell cycle progression. However, it remains unclear which stabilization function is essential for fork stability and whether specific sites in the genome depend on one function over the other.In an effort to test if an essential part of fork stabilization is mediated through inhibiting CDK-dependent pathways, such as inhibiting premature activation of the AURKA-PLK1 pathway, we established a system to hyper-activate the AURKA-PLK1 pathway to determine if it is sufficient to cause fork collapse. We found that fork collapse was not achievable solely through Aurora A overexpression nor with overexpression of its co-activators, TPX2 and BORA, but rather that CDK1 activation was also required. To test if CDK1-activation is sufficient to promote fork collapse, we inhibited WEE1, which short-circuits the cell cycle checkpoint function of ATR without inhibiting its fork-proximal activity. Using flow cytometry based fork collapse assays and genome-wide detection of RPA accumulation using RPA ChIP-Seq, we show that WEE1 and ATR inhibition cause similar levels of fork collapse at overlapping genomic locations in a CDK1-depdendent manner under conditions of partial replication inhibition (low dose aphidicolin). Notably, treatment with WEE1 inhibitor (WEE1i) alone was also sufficient to cause replication fork collapse, and did so more rapidly and to a higher degree than treatment with ATR inhibitor (ATRi) alone. Interestingly, clear differences in site specificity were observed when WEE1i was combined with ATRi, suggesting that particular sites in the genome may be slightly more dependent on the local functions of ATR than others. Thus, cell cycle checkpoint abrogation by WEE1i is sufficient to cause replication fork collapse in a manner similar to ATRi; however, site-specific roles for ATR remain. Together our findings indicate that the cell cycle checkpoint of ATR is key in stabilizing replication forks at a majority of sites in the genome. These findings could be leveraged to develop cancer treatments that exploit combinations of oncogenic genomic breakage signatures with that of WEE1 or ATR inhibitors.

Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2007 with total page 854 pages. Available in PDF, EPUB and Kindle. Book excerpt: MBC online publishes papers that describe and interpret results of original research conserning the molecular aspects of cell structure and function.

Download or read book DNA Replication Recombination and Repair written by Fumio Hanaoka and published by Springer. This book was released on 2016-01-22 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a comprehensive review of the detailed molecular mechanisms of and functional crosstalk among the replication, recombination, and repair of DNA (collectively called the "3Rs") and the related processes, with special consciousness of their biological and clinical consequences. The 3Rs are fundamental molecular mechanisms for organisms to maintain and sometimes intentionally alter genetic information. DNA replication, recombination, and repair, individually, have been important subjects of molecular biology since its emergence, but we have recently become aware that the 3Rs are actually much more intimately related to one another than we used to realize. Furthermore, the 3R research fields have been growing even more interdisciplinary, with better understanding of molecular mechanisms underlying other important processes, such as chromosome structures and functions, cell cycle and checkpoints, transcriptional and epigenetic regulation, and so on. This book comprises 7 parts and 21 chapters: Part 1 (Chapters 1–3), DNA Replication; Part 2 (Chapters 4–6), DNA Recombination; Part 3 (Chapters 7–9), DNA Repair; Part 4 (Chapters 10–13), Genome Instability and Mutagenesis; Part 5 (Chapters 14–15), Chromosome Dynamics and Functions; Part 6 (Chapters 16–18), Cell Cycle and Checkpoints; Part 7 (Chapters 19–21), Interplay with Transcription and Epigenetic Regulation. This volume should attract the great interest of graduate students, postdoctoral fellows, and senior scientists in broad research fields of basic molecular biology, not only the core 3Rs, but also the various related fields (chromosome, cell cycle, transcription, epigenetics, and similar areas). Additionally, researchers in neurological sciences, developmental biology, immunology, evolutionary biology, and many other fields will find this book valuable.

Download or read book DNA Replication written by Hisao Masai and published by Springer. This book was released on 2018-01-22 with total page 581 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews the latest trends and future directions of DNA replication research. The contents reflect upon the principles that have been established through the genetic and enzymatic studies of bacterial, viral, and cellular replication during the past decades. The book begins with a historical overview of the studies on eukaryotic DNA replication by Professor Thomas Kelly, a pioneer of the field. The following chapters include genome-wide studies of replication origins and initiation factor binding, as well as the timing of DNA replications, mechanisms of initiation, DNA chain elongation and termination of DNA replication, the structural basis of functions of protein complexes responsible for execution of DNA replication, cell cycle-dependent regulation of DNA replication, the nature of replication stress and cells’ strategy to deal with the stress, and finally how all these phenomena are interconnected to genome instability and development of various diseases. By reviewing the existing concepts ranging from the old principles to the newest ideas, the book gives readers an opportunity to learn how the classical replication principles are now being modified and new concepts are being generated to explain how genome DNA replication is achieved with such high adaptability and plasticity. With the development of new methods including cryoelectron microscopy analyses of huge protein complexes, single molecular analyses of initiation and elongation of DNA replication, and total reconstitution of eukaryotic DNA replication with purified factors, the field is enjoying one of its most exciting moments, and this highly timely book conveys that excitement to all interested readers.

Download or read book Plant Kinases written by Nico Dissmeyer and published by Humana Press. This book was released on 2011-08-26 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Modification of target protein properties by reversible phosphorylation events has been found to be one of the most prominent cellular control processes in all organisms. Recent advances in the areas of molecular biology and biochemistry are presenting new possibilities for reaching an unprecedented depth and a proteome-wide understanding of phosphorylation processes in plants as well as in other species. The major goal of Plant Kinases: Methods and Protocols is to provide the experimentalist with a detailed account of the practical steps necessary for successfully carrying out each protocol in his or her own laboratory. Plant protein kinases specifically addressed in this volume are members of the plant MAP kinase cascade, cyclin- and Calcium-dependent protein kinases, and plant sensor and receptor kinases. Written in the highly successful Methods in Molecular BiologyTM series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Plant Kinases: Methods and Protocols will prove a useful laboratory companion to both novice and seasoned researchers by facilitating the practical work that will lead them to new and exciting insights in this dynamic field.

Download or read book Breast Cancer written by Phuc Van Pham and published by BoD – Books on Demand. This book was released on 2017-04-05 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast Cancer - From Biology to Medicine thoroughly examines breast cancer from basic definitions, to cellular and molecular biology, to diagnosis and treatment. This book also has some additional focus on preclinical and clinical results in diagnosis and treatment of breast cancer. The book begins with introduction on epidemiology and pathophysiology of breast cancer in Section 1. In Section 2, the subsequent chapters introduce molecular and cellular biology of breast cancer with some particular signaling pathways, the gene expression, as well as the gene methylation and genomic imprinting, especially the existence of breast cancer stem cells. In Section 3, some new diagnostic methods and updated therapies from surgery, chemotherapy, hormone therapy, immunotherapy, radiotherapy, and some complementary therapies are discussed. This book provides a succinct yet comprehensive overview of breast cancer for advanced students, graduate students, and researchers as well as those working with breast cancer in a clinical setting.

Download or read book Stress Response Mechanisms in Fungi written by Marek Skoneczny and published by Springer. This book was released on 2019-12-10 with total page 259 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers both the molecular basics of fungal stress response strategies as well as biotechnological applications thereof. The complex regulatory mechanisms of stress response pathways are presented in a concise and well-readable manner. Also, light will be shed on the interconnection of pathways responding to different types of stress. Profound knowledge of stress responses in yeast and filamentous fungi is crucial for further optimization of industrial processes. Applications are manifold, for example in fungicide development, for improving the resistance of crop plants to fungal pathogens, but also in medicine to help curing fungal infections. The book targets researchers from academia and industry, as well as graduate students interested in microbiology, mycology and biomedicine.

Download or read book The Plant Cell Cycle written by Dirk Inzé and published by Springer Science & Business Media. This book was released on 2011-06-27 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, the study of the plant cell cycle has become of major interest, not only to scientists working on cell division sensu strictu , but also to scientists dealing with plant hormones, development and environmental effects on growth. The book The Plant Cell Cycle is a very timely contribution to this exploding field. Outstanding contributors reviewed, not only knowledge on the most important classes of cell cycle regulators, but also summarized the various processes in which cell cycle control plays a pivotal role. The central role of the cell cycle makes this book an absolute must for plant molecular biologists.

Download or read book NanoBioEngineering written by Bhupinder Singh and published by CRC Press. This book was released on 2018-11-02 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: The objective of this book is to provide the fundamental comprehension of a broad range of topics in an integrated volume such that readership hailing from diverse disciplines can rapidly acquire the necessary background for applying it in pertinent research and development field.

Download or read book Quadruplex Nucleic Acids written by Stephen Neidle and published by Royal Society of Chemistry. This book was released on 2007-10-31 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: Guanine rich DNA has been known for decades to form unusual structures, although their biological relevance was little understood. Recent advances have demonstrated that quadruplex structures can play a role in gene expression and provide opportunities for a new class of anticancer therapeutics. A number of quadruplex-specific proteins have also been discovered. Quadruplex Nucleic Acids discusses all aspects of the fundamentals of quadruplex structures, including their structure in solution and the crystalline state, the kinetics of quadruplex folding, and the role of cations in structure and stability. The biology of quadruplexes and G-rich genomic regions and G-quartets in supramolecular chemistry and nanoscience are also considered. Surveying the current state of knowledge, and with contributions from leading experts, this is the first comprehensive review of this rapidly growing area. Quadruplex Nucleic Acids is ideal for researchers interested in areas related to chemistry, chemical biology, medicinal chemistry, molecular pharmacology, and structural and molecular biology.

Download or read book Stem Cell Biology written by Daniel R. Marshak and published by CSHL Press. This book was released on 2001 with total page 566 pages. Available in PDF, EPUB and Kindle. Book excerpt: Stem cells are the focus of intense interest from a growing, multidisciplinary community of investigators with new tools for isolating and characterizing these elusive cell types. This volume, which features contributions from many of the world's leading laboratories, provides a uniquely broad and authoritative basis for understanding the biology of stem cells and the current excitement about their potential for clinical exploitation. It is an essential work of reference for investigators in embryology, hematology, and neurobiology, and their potential for clinical exploitation. It is an essential work of reference for investigators in embryology, hematology, and neurobiology, and their collaborators in the emerging field of regenerative medicine.

Download or read book Histological Typing of Ovarian Tumours written by Robert Edward Scully and published by Springer Science & Business Media. This book was released on 1999-04-23 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although the histological typing of ovarian tumours is the focus of this volume, other aspects of investigation of a specimen of ovarian tumour are also important. Some of these aspects are mentioned in the text or illustrated. They include tumour grading, which is impor­ tantprognostically and therapeutically for certain types ofovarian tu­ mour, quantification ofcomponents in mixed tumours and evaluation of the stroma of certain tumours that are associated with endocrine function. Grading methodologies have varied from one tumour type to another and from one group of investigators to another for the same type of tumour. Because a standard internationally recognized grading methodology has not been established, no specific guidance is presented in this volume. Nevertheless, grading by any generally acceptable method should be incorporated in the diagnosis whenever appropriate. The clinical and pathological classification of the extent of tu­ mour growth (staging) should be taken into account for the purposes of treatment and prognosis. The TNlV1/FIGO system is therefore in­ cluded (p. 45). Histological Classification of Ovarian Tumours 1 Surface Epithelial-Stromal Tumours 1. 1 Serous tumours 1. 1. 1 Benign 1 1. 1. 1. 1 Cystadenoma 8441/0 Papillary cystadenoma 8460/0 1. 1. 1. 2 Surface papilloma . . . . . . . . . . . . . . . . . . . . . . . . 8461/0 1. 1. 1. 3 Adenofibroma; cystadenofibroma . . . . . 9014/0 1. 1. 2 Of borderline malignancy (of low malignant potential) 2 1. 1. 2. 1 Cystic tumour 8442/1 Papillary cystic tumour . . . . . . . . . . . . . . . . . . . . 846211 Surface papillary tumour. . . . . . . . . . . . . . . . . . . 8463/1 1. 1. 2. 2 1. 1. 2. 3 Adenofibroma; cystadenofibroma 9014/1 1. 1.

Download or read book Telomeres and Telomerase in Cancer written by Keiko Hiyama and published by Springer Science & Business Media. This book was released on 2009-03-18 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.

Download or read book Chromosomal Alterations written by Günter Obe and published by Springer Science & Business Media. This book was released on 2007-06-02 with total page 526 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book helps the reader to better understand cytogenetics and the intricacies of the methodology. The different methods of fluorescence in situ hybridization are discussed and the results achieved are presented. The book provides a comprehensive review of basic and applied aspects of cytogenetics and thus is of intense interest to all those interested in chromosomes and their alterations by different types of mutagens, including chemical mutagens and ionizing and nonionizing radiation, with special reference to electromagnetic fields.

Download or read book Cosmetic Formulation written by Heather A.E. Benson and published by CRC Press. This book was released on 2019-04-05 with total page 479 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cosmetics are the most widely applied products to the skin and include creams, lotions, gels and sprays. Their formulation, design and manufacturing ranges from large cosmetic houses to small private companies. This book covers the current science in the formulations of cosmetics applied to the skin. It includes basic formulation, skin science, advanced formulation, and cosmetic product development, including both descriptive and mechanistic content with an emphasis on practical aspects. Key Features: Covers cosmetic products/formulation from theory to practice Includes case studies to illustrate real-life formulation development and problem solving Offers a practical, user-friendly approach, relying on the work of recognized experts in the field Provides insights into the future directions in cosmetic product development Presents basic formulation, skin science, advanced formulation and cosmetic product development

Download or read book Medical Terminology Made Incredibly Easy written by and published by Lippincott Williams & Wilkins. This book was released on 2008-06-01 with total page 436 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written in the award-winning, lighthearted Incredibly Easy! style, this book is an excellent aid to understanding and retention of medical terminology. The first chapter focuses on key concepts of medical terminology, including common word components. Subsequent chapters cover individual body systems, providing in-depth definitions that connect words to their meanings. This Third Edition features new chapters on obstetric and mental health terms and expanded "Pump Up Your Pronunciation" charts. Two eight-page full-color inserts offer a closer look at anatomical terminology. A companion Website offers student and instructor ancillaries including a pronunciation guide with hundreds of terms, "Pump Up Your Pronunciation" study cards, practice exercises, PowerPoint presentations, and a test generator. Online Tutoring powered by Smarthinking--Online tutoring, powered by Smarthinking, gives students access to expert nursing and allied health science educators whose mission, like yours, is to achieve success. Students can access live tutoring support, critiques of written work, and other valuable tools.

Download or read book Cell Senescence written by Lorenzo Galluzzi and published by Humana Press. This book was released on 2013-01-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cell senescence is the process whereby cells permanently lose the possibility to proliferate without undergoing cell death, and occurs in a plethora of distinct model organisms. In Cell Senescence: Methods and Protocols, expert researchers in the field detail the methods that are now commonly used to study cell senescence, in model organisms encompassing bacteria, fungi, worms, flies, zebrafish, and mammalian cells. These techniques cover the study of all the morphological, biochemical and functional manifestations of senescence at the cellular level and include protocols for population analyses and high-throughput approaches in suitable model organisms. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.