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Signalling DNA Damage (Book chapter)

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ISBN: 9789535107378 Year: DOI: 10.5772/50863 Language: English
Publisher: IntechOpen Grant: FP7 Ideas: European Research Council - 210520
Subject: Science (General)
Added to DOAB on : 2019-01-17 11:47:57
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During our lifetime, the genome is constantly being exposed to different types of damage caused either by exogenous sources (radiations and/or genotoxic compound) but also as byproducts of endogenous processes (reactive oxigen species during respiration, stalled forks during replication, eroded telomeres, etc). From a structural point of view, there are many types of DNA damage including single or double strand breaks, base modifications and losses or base-pair mismatches. The amount of lesions that we face is enormous with estimates suggesting that each of our 1013 cells has to deal with around 10.000 lesions per day [1]. While the majority of these events are properly resolved by specialized mechanisms, a deficient response to DNA damage, and particularly to DSB, harbors a serious threat to human health [2].&#xD;&#xD;DSB can be formed [1] following an exposure to ionizing radiation (X- or γ-rays) or clastogenic drugs; [2] endogenously, during DNA replication, or [3], as a consequence of reactive oxygen species (ROS) generated during oxidative metabolism. In addition, programmed DSB are used as repair intermediates during V(D)J and Class-Switch recombination (CSR) in lymphocytes [3], or during meiotic recombination [4]. Because of this, immunodeficiency and/or sterility problems are frequently associated with DDR-related pathologies.

Keywords

dna damage

DNA Polymerases in Biotechnology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194551 Year: Pages: 146 DOI: 10.3389/978-2-88919-455-1 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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DNA polymerases are core tools for molecular biology including PCR, whole genome amplification, DNA sequencing and genotyping. Research has focused on discovery of novel DNA polymerases, characterization of DNA polymerase biochemistry and development of new replication assays. These studies have accelerated DNA polymerase engineering for biotechnology. For example, DNA polymerases have been engineered for increased speed and fidelity in PCR while lowering amplification sequence bias. Inhibitor resistant DNA polymerase variants enable PCR directly from tissue (i.e. blood). Design of DNA polymerases that efficiently incorporate modified nucleotide have been critical for development of next generation DNA sequencing, synthetic biology and other labeling and detection technologies. The Frontiers in Microbiology Research Topic on DNA polymerases in Biotechnology aims to capture current research on DNA polymerases and their use in emerging technologies.

DNA Replication Controls

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ISBN: 9783038425724 9783038425731 Year: Volume: 2 Pages: X, 346 DOI: 10.3390/books978-3-03842-573-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-12-27 08:38:10
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The conditions for DNA replication are not ideal, owing to endogenous and exogenous replication stresses that lead to arrest of the replication fork. Arrested forks are among the most serious threats to genomic integrity because they can break or rearrange, leading to genomic instability, which is a hallmark of cancers and aging-related disorders. This title, “DNA Replication Controls”, presents series of new reviews and original research articles, providing a comprehensive guide to theoretical advancements in the field of DNA replication research in both prokaryotic and eukaryotic systems. The topics include DNA polymerases and helicases; replication initiation; replication timing; replication-associated DNA repair; and replication of difficult-to-replicate genomic regions, including telomeres, centromeres and highly-transcribed regions. This title also provides recent advancements in studies of cellular processes that are coordinated with DNA replication and how defects in the DNA replication program result in genetic disorders, including cancer. Written by leading experts in DNA replication regulation, this book will be an important resource for a wide variety of audiences, including junior graduate students and established investigators who have interests in DNA replication and genome maintenance mechanisms.

DNA Replication Controls

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ISBN: 9783038425687 9783038425694 Year: Volume: 1 Pages: X, 304 DOI: 10.3390/books978-3-03842-569-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2018-01-02 15:17:59
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The conditions for DNA replication are not ideal, owing to endogenous and exogenous replication stresses that lead to arrest of the replication fork. Arrested forks are among the most serious threats to genomic integrity because they can break or rearrange, leading to genomic instability, which is a hallmark of cancers and aging-related disorders.

Grappling with the Multifaceted World of the DNA Damage Response

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450572 Year: Pages: 306 DOI: 10.3389/978-2-88945-057-2 Language: English
Publisher: Frontiers Media SA
Subject: Genetics --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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DNA damage is a major threat to genomic integrity and cell survival. It can arise both spontaneously and in response to exogenous agents. DNA damage can attack most parts of the DNA structure, ranging from minor and major chemical modifications, to single-strand breaks (SSBs) and gaps, to full double-strand breaks (DSBs). If DNA injuries are mis-repaired or unrepaired, they may ultimately result in mutations or wider-scale genome aberrations that threaten cell homeostasis. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. This Research Topic was aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes.DNA damage is a major threat to genomic integrity and cell survival. It can arise both spontaneously and in response to exogenous agents. DNA damage can attack most parts of the DNA structure, ranging from minor and major chemical modifications, to single-strand breaks (SSBs) and gaps, to full double-strand breaks (DSBs). If DNA injuries are mis-repaired or unrepaired, they may ultimately result in mutations or wider-scale genome aberrations that threaten cell homeostasis. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. This Research Topic was aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes.

Mobile Genetic Elements in Cellular Differentiation, Genome Stability, and Cancer

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453894 Year: Pages: 123 DOI: 10.3389/978-2-88945-389-4 Language: English
Publisher: Frontiers Media SA
Subject: Biology --- Science (General) --- Chemistry (General)
Added to DOAB on : 2018-11-22 11:50:10
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The human genome, as with the genome of most organisms, is comprised of various types of mobile genetic element derived repeats. Mobile genetic elements that mobilize by an RNA intermediate, include both autonomous and non-autonomous retrotransposons, and mobilize by a “copy and paste” mechanism that relies of the presence of a functional reverse transcriptase activity. The extent to which these different types of elements are actively mobilizing varies among organisms, as revealed with the advent of Next Generation DNA sequencing (NGS).To understand the normal and aberrant mechanisms that impact the mobility of these elements requires a more extensive understanding of how these elements interact with molecular pathways of the cell, including DNA repair, recombination and chromatin. In addition, epigenetic based-mechanisms can also influence the mobility of these elements, likely by transcriptional activation or repression in certain cell types. Studies regarding how mobile genetic elements interface and evolve with these pathways will rely on genomic studies from various model organisms. In addition, the mechanistic details of how these elements are regulated will continue to be elucidated with the use of genetic, biochemical, molecular, cellular, and bioinformatic approaches. Remarkably, the current understanding regarding the biology of these elements in the human genome, suggests these elements may impact developmental biology, including cellular differentiation, neuronal development, and immune function. Thus, aberrant changes in these molecular pathways may also impact disease, including neuronal degeneration, autoimmunity, and cancer.

DNA helicases: expression, functions and clinical implications

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195756 Year: Pages: 78 DOI: 10.3389/978-2-88919-575-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2015-10-30 16:33:44
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Helicases are the proteins that bind to double- or single-stranded DNA and/or RNA chains to unwind higher order structures, usually consuming energy from the hydrolysis of ATP molecules. The biological roles of helicases are associated with a variety of DNA and/or RNA metabolisms, including DNA-replication, -repair, -recombination, RNA processing, and transcription. Dysfunctions of helicases cause various diseases, such as xeroderma pigmentosum (XP), premature aging syndrome, cancer and immunodeficiency, in humans. Moreover, recent genetic analyses revealed that mutations in helicase-encoding genes are frequently found in patients of specific diseases. Some helicases regulate cellular senescence by controlling integrity of genomes, and others play a role in neuromuscular functions presumably by modulating processing of mRNAs. However, the molecular mechanisms of how helicases are regulated in order to maintain our health are not yet fully understood. In this research topic, we will focus on the expression and functions of helicases and their encoding genes, reviewing recent research progresses that provide new insights into development of clinical and pharmaceutical treatments targeting helicases.

Keywords

Aging --- Cancer --- DNA Repair --- helicases --- Telomere

DNA, statistics and the law: a cross-disciplinary approach to forensic inference

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192502 Year: Pages: 39 DOI: 10.3389/978-2-88919-250-2 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2015-11-16 15:44:59
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From ABO typing during the first half of the 20th century, to the use of enzymes and protein contained in blood serums and finally direct DNA typing, biology has been serving forensic purposes for many decades. Statistics, in turn, has been constantly underpinning the discussions of the probative value of results of biological analyses, in particular when defendants could not be considered as excluded as potential sources because of different genetic traits. The marriage between genetics and statistics has never been an easy one, though, as is illustrated by fierce arguments that peaked in the so-called "DNA wars" in some American courtrooms in the mid-1990s. This controversy has contributed to a lively production of research and publications on various interpretative topics, such as the collection of relevant data, foundations in population genetics as well as theoretical and practical considerations in probability and statistics. Both DNA profiling as a technique and the associated statistical considerations are now widely accepted as robust, but this does not yet guarantee or imply a neat transition to their application in court. Indeed, statistical principles applied to results of forensic DNA profiling analyses are a necessary, yet not a sufficient preliminary requirement for the contextually meaningful use of DNA in the law. Ultimately, the appropriate use of DNA in the forensic context relies on inference, i.e. reasoning reasonably in the face of uncertainty. This is all the more challenging that such thought processes need to be adopted by stakeholders from various backgrounds and holding diverse interests. Although several topics of the DNA controversy have been settled over time, some others are still debated (such as the question of how to deal with the probability of error), while yet others - purportedly settled topics - saw some recent revivals (e.g., the question of how to deal with database searches). In addition, new challenging topics have emerged over the last decade, such as the analysis and interpretation of traces containing only low quantities of DNA where artefacts of varying nature may affect results. Both technical and interpretative research involving statistics thus represent areas where ongoing research is necessary, and where scholars from the natural sciences and the law should collaborate. The articles in this Research Topic thus aim to investigate, from an interdisciplinary perspective, the current understanding of the strengths and limitations of DNA profiling results in legal applications. This Research Topic accepts contributions in all frontiers article type categories and places an emphasis on topics with a multidisciplinary perspective that explore (while not being limited to) statistical genetics for forensic scientists, case studies and reports, evaluation and interpretation of forensic findings, communication of expert findings to laypersons, quantitative legal reasoning and fact-finding using probability.

Epigenetic pathways in PTSD: How traumatic experiences leave their signature on the genome

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194582 Year: Pages: 158 DOI: 10.3389/978-2-88919-458-2 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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This research topic focuses on epigenetic components of PTSD. Epigenetic mechanisms are a class of molecular mechanisms by which environmental influences, including stress, can interact with the genome to have long-term consequences for brain plasticity and behavior. Articles herein include empirical reports and reviews that link stress and trauma with epigenetic alterations in humans and animal models of early- or later-life stress. Themes present throughout the collection include: DNA methylation is a useful biomarker of stress and treatment outcome in humans; epigenetic programming of stress-sensitive physiological systems early in development confers an enhanced risk on disease development upon re-exposure to trauma or stress; and, long-lived fear memories are associated with epigenetic alterations in fear memory and extinction brain circuitry.

Keywords

DNA Methylation --- Histones --- miRNA --- stress --- Fear --- PTSD

Epigenetik

Authors: ---
ISBN: 9783845270838 Year: DOI: http://dx.doi.org/10.5771/9783845270838 Language: de
Publisher: Nomos Verlagsgesellschaft mbH & Co. KG
Subject: Law
Added to DOAB on : 2019-03-26 14:01:47
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Do the mechanisms of epigenetics control our genes? Or maybe not? The field of epigenetics investigates the complex molecular interaction of genes and their physical environment. Epigenetic mechanisms can alter our DNA structurally, change gene expression and thus drive cellular development throughout life. They have currently been associated with numerous diseases and are known to shape both appearance and behavioral patterns. Environmental factors as well as lifestyle choices come into play and impart their

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