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Maintenance of Genome Integrity: DNA Damage Sensing, Signaling, Repair and Replication in Plants

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198207 Year: Pages: 129 DOI: 10.3389/978-2-88919-820-7 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Environmental stresses and metabolic by-products can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. As a consequence, plant growth and productivity are irreversibly compromised. To overcome genotoxic injury, plants have evolved complex strategies relying on a highly efficient repair machinery that responds to sophisticated damage perception/signaling networks. The DNA damage signaling network contains several key components: DNA damage sensors, signal transducers, mediators, and effectors. Most of these components are common to other eukaryotes but some features are unique to the plant kingdom. ATM and ATR are well-conserved members of PIKK family, which amplify and transduce signals to downstream effectors. ATM primarily responds to DNA double strand breaks while ATR responds to various forms of DNA damage. The signals from the activated transducer kinases are transmitted to the downstream cell-cycle regulators, such as CHK1, CHK2, and p53 in many eukaryotes. However, plants have no homologue of CHK1, CHK2 nor p53. The finding of Arabidopsis transcription factor SOG1 that seems functionally but not structurally similar to p53 suggests that plants have developed unique cell cycle regulation mechanism. The double strand break repair, recombination repair, postreplication repair, and lesion bypass, have been investigated in several plants. The DNA double strand break, a most critical damage for organisms are repaired non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Damage on template DNA makes replication stall, which is processed by translesion synthesis (TLS) or error-free postreplication repair (PPR) pathway. Deletion of the error-prone TLS polymerase reduces mutation frequencies, suggesting PPR maintains the stalled replication fork when TLS is not available. Unveiling the regulation networks among these multiple pathways would be the next challenge to be completed. Some intriguing issues have been disclosed such as the cross-talk between DNA repair, senescence and pathogen response and the involvement of non-coding RNAs in global genome stability. Several studies have highlighted the essential contribution of chromatin remodeling in DNA repair. DNA damage sensing, signaling and repair have been investigated in relation to environmental stresses, seed quality issues, mutation breeding in both model and crop plants and all these studies strengthen the idea that components of the plant response to genotoxic stress might represent tools to improve stress tolerance and field performance. This focus issue gives researchers the opportunity to gather and interact by providing Mini-Reviews, Commentaries, Opinions, Original Research and Method articles which describe the most recent advances and future perspectives in the field of DNA damage sensing, signaling and repair in plants. A comprehensive overview of the current progresses dealing with the genotoxic stress response in plants will be provided looking at cellular and molecular level with multidisciplinary approaches. This will hopefully bring together valuable information for both plant biotechnologists and breeders.

Cell Fate

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198528 Year: Pages: 102 DOI: 10.3389/978-2-88919-852-8 Language: English
Publisher: Frontiers Media SA
Subject: Genetics --- Science (General)
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The fundamental question of how an undifferentiated progenitor cell adopts a more specialized cell fate that then contributes to the development of specialized tissues, organs, organ systems and ultimately a unique individual of a given species has intrigued cell and developmental biologists for many years. Advances in molecular and cell biology have enabled investigators to identify genetic and epigenetic factors that contribute to these processes with increasing detail and also to define the various molecular characteristics of each cell fate with greater precision. Understanding these processes have also provided greater insights into disorders in which the normal mechanisms of cell fate determination are altered, such as in cancer and inherited malformations. With these advances have come techniques that facilitate the manipulation of cell fate, which have the potential to revolutionize the field of medicine by facilitating the repair and/or regeneration of diseased organs. Given the rapid advances that are occurring in the field, the articles in this eBook are both relevant and timely. These articles originally appeared online as part of the Research Topic “Cell Fate” overseen by my colleagues Dr. Lin, Dr. Buttitta, Dr. Maves, Dr. Dilworth, Dr. Paladini and myself and have been viewed extensively. Because of their popularity, they are now made available as an eBook, in a more easily downloadable form.Michael T. Chin

Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199495 Year: Pages: 107 DOI: 10.3389/978-2-88919-949-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
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For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: ‘Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets’ we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the ‘DNA damage response (DDR)’ cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.

In vivo Cell Biology of Cerebral Cortical Development and Its Related Neurological Disorders: Cellular Insights into Neurogenesis and Neuronal Migration

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199624 Year: Pages: 268 DOI: 10.3389/978-2-88919-962-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
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The brain consists of a complex but precisely organized neural network, which provides the structural basis of higher order functions. Such a complex structure originates from a simple pseudostratified neuroepithelium. During the developing mammalian cerebral cortex, a cohort of neural progenitors, located near the ventricle, differentiates into neurons and exhibits multi-step modes of migration toward the pial surface. Tight regulation of neurogenesis and neuronal migration is essential for the determination of the neuron number in adult brains and the proper positioning of excitatory and inhibitory neurons in a specific layer, respectively. In addition, defects in neurogenesis and neuronal migration can cause several neurological disorders, such as microcephaly, periventricular heterotopia and lissencephaly. Recent advances in genetic approaches to study the developing cerebral cortex, as well as the use of a number of novel techniques, particularly in vivo electroporation and time-lapse analyses using explant slice cultures, have significantly increased our understanding of cortical development. These novel techniques have allowed for cell biological analyses of cerebral cortical development in vivo or ex vivo, showing that many cellular events, including endocytosis, cell adhesion, microtubule and actin cytoskeletal regulation, neurotransmitter release, stress response, the consequence of cellular crowding (physical force), dynamics of transcription factors, midbody release and polarity transition are required for neurogenesis and/or neuronal migration. The aim of this research topic is to highlight molecular and cellular mechanisms underlying cerebral cortical development and its related neurological disorders from the cell biological point of views, such as cell division, cell-cycle regulation, cytoskeletal organization, cell adhesion and membrane trafficking. The topic has been organized into three chapters: 1) neurogenesis and cell fate determination, 2) neuronal migration and 3) cortical development-related neurological disorders. We hope that the results and discussions contributed by all authors in this research topic will be broadly useful for further advances in basic research, as well as improvements in the etiology and care of patients suffering from neurological and psychiatric disorders.

Transcriptional Regulation in Cancers and Metabolic Diseases

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197125 Year: Pages: 98 DOI: 10.3389/978-2-88919-712-5 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General) --- Internal medicine
Added to DOAB on : 2016-04-07 11:22:02
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The transcription factor (TF) mediated regulation of gene expression is a process fundamental to all biological and physiological processes. Genetic changes and epigenetic modifications of TFs affect target gene expression during the formation of malignant cells. Extensive work has been done on the critical TFs in various disease models. Despite the success of numerous TF-targeted therapies, there remain significant hurdles understanding the mechanisms, transcriptional targets and networks of physiologic pathways that govern TF action. This effort is now beginning to produce exciting new avenues of research. A clinically relevant topic for genetic change of TF is the mutant isoforms of p53, the most famous tumor suppressor. The p53 mutations either results in loss of function, or acting as dominant negative for wild-type protein, or ‘gain of function’ specifically promoting cancer survival. The gain of function is achieved by shifting p53 binding partner proteins, or changed genomic binding landscape leading to a cancer-promoting transcriptome. Another example of genetic change of TF causing malignancy is the AML-ETO fusion protein in the human t(8;21)-leukemia. The fusion protein is an active TF, and more interestingly, new studies link the disease causing role of AML-ETO to the unique transcriptome in the hematopoietic stem cells. Nuclear receptors (NR) are a group of ligand-dependent TFs governing the expression of genes involved in a broad range of reproductive, developmental and metabolic programs. Genetic changes and epigenetic modifications of NRs lead to cancers and metabolic diseases. Androgen receptor (AR), estrogen receptor (ER) and progesterone receptor (PR) are well studied NRs in prostate, breast and endometrial cancers. The development in sequencing technology and computational genomics enable us to investigate the transcription programs of these master TFs in an unprecedented level. This Research Topic aims to present the most up-to-date progress in the field of transcription regulation in cancers and metabolic diseases.

The Origin of the Plasma Cell Heterogeneity

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197347 Year: Pages: 80 DOI: 10.3389/978-2-88919-734-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Plasma cells (PCs) are terminally differentiated B-cells producing large amounts of immunoglobulins (Ig). In humans, most of circulating Ig are produced by bone marrow plasma cells. PCs differentiate from activated naïve or memory B-cells usually activated by specific antigens. It is still controversial whether the regulation of PCs numbers and the “active” in vivo Ig diversity depend or not on non-specific reactivation of B-cells during infections. Depending on the stimulus (T-independent/T-dependent antigen, cytokines, partner cells) and B-cell types (naïve or memory, circulating or germinal center, lymph nodes or spleen, B1 or B2...), both the phenotype and isotype of PCs differ suggesting that PC diversity is either linked to B-cell diversity or to the type of stimulus or to both. Knowledge of the mechanisms supporting PC diversity has important consequences for the management of i) plasma cell neoplasia such as Multiple Myeloma and Waldenström's Macroglobulinemia, ii) vaccine protection against pathogens and iii) auto-immune diseases.

Keywords

Plasma cell --- B-cell --- differentiation --- Cell Cycle --- IL21 --- Autophagy --- B1 --- Autoimmunity --- Myeloma

Advances in Seed Biology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196753 Year: Pages: 238 DOI: 10.3389/978-2-88919-675-3 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2016-08-16 10:34:25
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The seed plays a fundamental role in plant reproduction as well as a key source of energy, nutrients and raw materials for developing and sustaining humanity. With an expanding and generally more affluent world population projected to reach nine billion by mid-century, coupled to diminishing availability of inputs, agriculture is facing increasing challenges to ensure sufficient grain production. A deeper understanding of seed development, evolution and physiology will undoubtedly provide a fundamental basis to improve plant breeding practices and ultimately crop yields. Recent advances in genetic, biochemical, molecular and physiological research, mostly brought about by the deployment of novel high-throughput and high-sensitivity technologies, have begun to uncover and connect the molecular networks that control and integrate different aspects of seed development and help determine the economic value of grain crops with unprecedented details. The objective of this e-book is to provide a compilation of original research articles, reviews, hypotheses and perspectives that have recently been published in Frontiers in Plant Science, Plant Evolution and Development as part of the Research Topic entitled "Advances in Seed Biology". Editing this Research Topic has been an extremely interesting, educational and rewarding experience, and we sincerely thank all authors who contributed their expertise and in-depth knowledge of the different topics discussed. We hope that the information presented here will help to establish the state of the art of this field and will convey how exciting and important studying seeds is and hopefully will stimulate a new crop of scientists devoted to investigating the biology of seeds.

The Bacterial Cell: Coupling between Growth, Nucleoid Replication, Cell Division and Shape

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198177 Year: Pages: 324 DOI: 10.3389/978-2-88919-817-7 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
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Bacterial Physiology was inaugurated as a discipline by the seminal research of Maaløe, Schaechter and Kjeldgaard published in 1958. Their work clarified the relationship between cell composition and growth rate and led to unravel the temporal coupling between chromosome replication and the subsequent cell division by Helmstetter et al. a decade later. Now, after half a century this field has become a major research direction that attracts interest of many scientists from different disciplines. The outstanding question how the most basic cellular processes - mass growth, chromosome replication and cell division - are inter-coordinated in both space and time is still unresolved at the molecular level. Several particularly pertinent questions that are intensively studied follow: (a) what is the primary signal to place the Z-ring precisely between the two replicating and segregating nucleoids? (b) Is this coupling related to the structure and position of the nucleoid itself? (c) How does a bacterium determine and maintain its shape and dimensions? Possible answers include gene expression-based mechanisms, self-organization of protein assemblies and physical principles such as micro-phase separations by excluded volume interactions, diffusion ratchets and membrane stress or curvature. The relationships between biochemical reactions and physical forces are yet to be conceived and discovered. This e-book discusses the above mentioned and related questions. The book also serves as an important depository for state-of-the-art technologies, methods, theoretical simulations and innovative ideas and hypotheses for future testing. Integrating the information gained from various angles will likely help decipher how a relatively simple cell such as a bacterium incorporates its multitude of pathways and processes into a highly efficient self-organized system. The knowledge may be helpful in the ambition to artificially reconstruct a simple living system and to develop new antibacterial drugs.

DNA Replication Origins in Microbial Genomes

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197798 Year: Pages: 115 DOI: 10.3389/978-2-88919-779-8 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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DNA replication, a central event for cell proliferation, is the basis of biological inheritance. Complete and accurate DNA replication is integral to the maintenance of the genetic integrity of organisms. In all three domains of life, DNA replication begins at replication origins. In bacteria, replication typically initiates from a single replication origin (oriC), which contains several DnaA boxes and the AT-rich DNA unwinding element (DUE). In eukaryotic genomes, replication initiates from significantly more replication origins, activated simultaneously at a specific time. For eukaryotic organisms, replication origins are best characterized in the unicellular eukaryote budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. The budding yeast origins contain an essential sequence element called the ARS (autonomously replicating sequence), while the fission yeast origins consist of AT-rich sequences. Within the archaeal domain, the multiple replication origins have been identified by a predict-and-verify approach in the hyperthermophilic archaeon Sulfolobus. The basic structure of replication origins is conserved among archaea, typically including an AT-rich unwinding region flanked by several short repetitive DNA sequences, known as origin recognition boxes (ORBs). It appears that archaea have a simplified version of the eukaryotic replication apparatus, which has led to considerable interest in the archaeal machinery as a model of that in eukaryotes. The research on replication origins is important not only in providing insights into the structure and function of the replication origins but also in understanding the regulatory mechanisms of the initiation step in DNA replication. Therefore, intensive studies have been carried out in the last two decades. The pioneer work to identify bacterial oriCs in silico is the GC-skew analysis. Later, a method of cumulative GC skew without sliding windows was proposed to give better resolution. Meanwhile, an oligomer-skew method was also proposed to predict oriC regions in bacterial genomes. As a unique representation of a DNA sequence, the Z-curve method has been proved to be an accurate and effective approach to predict bacterial and archaeal replication origins. Budding yeast origins have been predicted by Oriscan using similarity to the characterized ones, while the fission yeast origins have been identified initially from AT content calculation. In comparison with the in silico analysis, the experimental methods are time-consuming and labor-intensive, but convincing and reliable. To identify microbial replication origins in vivo or in vitro, a number of experimental methods have been used including construction of replicative oriC plasmids, microarray-based or high-throughput sequencing-based marker frequency analysis, two-dimensional gel electrophoresis analysis and replication initiation point mapping (RIP mapping). The recent genome-wide approaches to identify and characterize replication origin locations have boosted the number of mapped yeast replication origins. In addition, the availability of increasing complete microbial genomes and emerging approaches has created challenges and opportunities for identification of their replication origins in silico, as well as in vivo and in vitro. The Frontiers in Microbiology Research Topic on DNA replication origins in microbial genomes is devoted to address the issues mentioned above, and aims to provide a comprehensive overview of current research in this field.

Mechanisms of Mitotic Chromosome Segregation

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ISBN: 9783038424031 9783038424024 Year: Pages: VIII, 332 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-05-10 09:52:09
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This book describes current knowledge about the mechanisms by which cells segregate their already duplicated chromosomes in preparation for cell division. Experts in the field treat several important aspects of this subject: (1) the history of research on mitotic mechanisms, to serve as a background; (2) assembly of the mitotic spindle; (3) Kinetochore assembly and function; (4) the mechanisms of chromosome congression to the metaphase plate; (5) the spindle assembly checkpoint; (6) mechanisms to avoid and correct erroneous chromosome attachments to the spindle; (7) a molecular perspective on spindle assembly in land plants; (8) chromosome segregation in anaphase A; (9) spindle elongation in anaphase B; and (10) the consequences of errors in chromosome segregation. Each chapter provides the reader with a comprehensive and accurate picture of current research in a form that is both readable and authoritative. The volume is suitable for scholars in this and related fields and for teaching at an advanced level.

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