The sciences of genetics and genomics are revealing more all the time regarding our statuses as individuals relative to our particular genomes. Geographical isolation is presumably the greatest factor in allowing for populations of a species to change genetically over time, in response to environmental pressures and genetic drift accelerated by the mechanism of sexual reproduction. In order to develop a robust account of what rights individual members of the human species might have to either their own particular DNA or (...) the human genome in general, one need to explain the relations between individuals and species in regards to deoxyribonucleic acid (DNA). The fact that genes carry over from species to species does not mean that those genes are completely identical across all species. Laws and regulations exist that govern the use of human tissues and property rights over their products. (shrink)

DNA barcodes, like traditional sources of taxonomic information, are potentially powerful heuristics in the identification of described species but require mindful analytical interpretation. The role of DNA barcoding in generating hypotheses of new taxa in need of formal taxonomic treatment is discussed, and it is emphasized that the recursive process of character evaluation is both necessary and best served by understanding the empirical mechanics of the discovery process. These undertakings carry enormous ramifications not only for the translation of DNA sequence (...) data into taxonomic information but also for our comprehension of the magnitude of species diversity and its disappearance. This paper examines the potential strengths and pitfalls of integrating DNA sequence data, specifically in the form of DNA barcodes as they are currently generated and analyzed, with taxonomic practice. (shrink)

Under the terms of the UN Convention on the Rights of the Child, which Australia has ratified, children have a right to know who their genetic parents are. As a result, we have a duty to establish these facts and to make this information available for children to access should they wish to know. Introducing mandatory DNA testing of newborns and their alleged genetic parents is one viable option to ensure that this information is available for children to access. Indeed, (...) it may be the only viable option to address childrens' right to the fulfilment of Article 7 of the CRC. There are a number of benefits to obtaining this benefit for children. For one, mandatory DNA testing could solve all disputed paternity cases and finalise them early in the lives of children, thus making life more financially secure for those children in the long term. This could reduce or eliminate the need for fathers to secretly carry out DNA tests in order to disestablish paternity. The large number of benefits gained from identifying genetic parents for children and the small possible risks that they may suffer when this information is withheld give us good reasons to support mandatory DNA testing. (shrink)

This chapter contains sections titled: Individuals and Species Commonalities among Species Individuals within Species Individual Histories and Individual Genomes The Social and Legal Importance of Individuality Human Individuals, Persons, and Rights Implications for Justice.

DNA topoisomerases, capable of manipulating DNA topology, are ubiquitous and indispensable for cellular survival due to the numerous roles they play during DNA metabolism. As we review here, current structural approaches have revealed unprecedented insights into the complex DNA‐topoisomerase interaction and strand passage mechanism, helping to advance our understanding of their activities in vivo. This has been complemented by single‐molecule techniques, which have facilitated the detailed dissection of the various topoisomerase reactions. Recent work has also revealed the importance of topoisomerase (...) interactions with accessory proteins and other DNA‐associated proteins, supporting the idea that they often function as part of multi‐enzyme assemblies in vivo. In addition, novel topoisomerases have been identified and explored, such as topo VIII and Mini‐A. These new findings are advancing our understanding of DNA‐related processes and the vital functions topos fulfil, demonstrating their indispensability in virtually every aspect of DNA metabolism. (shrink)

For nearly two decades, nonengineered human DNA was patented without challenge. The US Supreme Court recently agreed that many of those patents do not fit accurately into any currently accepted scheme of intellectual property protection. One should consider: whether DNA fits into other forms of property protection (land, moveables, chattels, etc.); whether DNA warrants a new and unique form of property protection, or whether DNA belongs to the class of objects generally considered to be as “the commons.” Current schemes of (...) patent protection for genes are entirely new, unwarranted by precedent, and utterly aberrant in applying the law of patent. Nonetheless, it bears examining how intellectual property schemes might serve as guidance for new forms of intellectual property protection for genes, if indeed those genes fit into classical dimensions of intellectual property. Private ownership of property has emerged as the dominant legal institution covering modes of possession. (shrink)

This chapter contains sections titled: Current Schemes of Intellectual Property Protection Existing Forms of Property Protection Brute Facts and Genes Unique Property Protection for DNA? The Notion of the Commons The Commons as a Choice The Commons by Necessity DNA as a Commons Is DNA More like Ideas or Radio Spectra?

Mortal and immortal DNA : Craig Venter and the lure of "lamia" -- Homeopathy : Holmes, hogwarts, and the Prince of Wales -- Citizen Pinel and the madman at Bellevue -- The experimental pathology of stress : Hans Selye to Paris Hilton -- Gore's fever and Dante's Inferno : Chikungunya reaches Ravenna -- Giving things their proper names : Carl Linnaeus and W.H. Auden -- Spinal irritation and fibromyalgia : Lincoln's surgeon general and the three graces -- Tithonus and the (...) fruit fly : new science and old myths -- Swiftboating "America the beautiful" : Katharine Lee Bates and a Boston marriage -- Nothing makes sense in medicine except in the light of biology -- Apply directly to the forehead : Holmes, Zola, and Hennapecia -- Elizabeth Blackwell breaks the bonds -- Chronic lyme disease and medically unexplained syndromes -- Eugenics and the immigrant : Rosalyn Yalow and Rita Levi-Montalcini -- Science in the Middle East : Robert Koch and the cholera war -- How to win a Nobel prize : thinking inside and outside the box -- Homer Smith and the lungfish : the last gasp of intelligent design -- DDT is back : let us spray! -- Academic boycotts and the Royal Society -- Teach evolution, learn science : John William Draper and the "bone bill" -- Diderot and the yeti crab : the encyclopedias of life -- Dengue fever in Rio : Macumba versus Voltaire. (shrink)

This paper focuses on the question of whether DNA patents help or hinder scientific discovery and innovation. While DNA patents create a wide variety of possible benefits and harms for science and technology, the evidence we have at this point in time supports the conclusion that they will probably promote rather than hamper scientific discovery and innovation. However, since DNA patenting is a relatively recent phenomena and the biotechnology industry is in its infancy, we should continue to gather evidence about (...) the effects of DNA patenting on scientific innovation and discovery as well the economic, social, and legal conditions relating to intellectual property in biotechnology. We should give the free market, the courts, researchers, and patent offices a chance to settle issues related to innovation and discovery, before we seek legislative remedies, since new laws proposed at this point would lack adequate foresight and could do more harm than good. However, we should be open to new laws or regulations on DNA patents if they are required to in order to deal with some of the biases and limitations of the free market. (shrink)

DNA methylation is a repressive epigenetic mark vital for normal development. Recent studies have uncovered an unexpected role for the DNA methylome in ensuring the correct targeting of the Polycomb repressive complexes throughout the genome. Here, we discuss the implications of these findings for cancer, where DNA methylation patterns are widely reprogrammed. We speculate that cancer‐associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes. As the Polycomb system is responsible for (...) the regulation of genes with key roles in cell fate decisions and cell cycle regulation, DNA methylation induced Polycomb mis‐targeting could directly drive carcinogenesis and disease progression.Editor's suggested further reading in BioEssays Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition Abstract. (shrink)

Through analysis of film sequences focusing on DNA in two British Broadcasting Corporation nonfiction science television programs, Wonders of Life and Bang! Goes the Theory, first broadcast in 2013, contrasting “religious” and “secular” representations of science are identified. In the “religious” portrayal, immutable scientific knowledge is revealed to humanity by nature with minimal human intervention. Science provides a creation story, “explanatory omnicompetence,” and makes life existentially meaningful. In the “secular” portrayal, scientific knowledge is changeable; is produced through technical skill in (...) expert communities; and is ambiguous, potentially positive and negative for society. Television representations of science affect audience understandings, and this is particularly the case for nonfiction representations of science, as they are likely to be “taken more seriously” than fictional representations. The consequences of the “religious” representation of science are discussed, and it is argued that a widespread understanding of science as presented in the religious portrayal would negatively impact democracy. (shrink)

The nuclear pore complex (NPC) is emerging as a center for recruitment of a class of “difficult to repair” lesions such as double‐strand breaks without a repair template and eroded telomeres in telomerase‐deficient cells. In addition to such pathological situations, a recent study by Su and colleagues shows that also physiological threats to genome integrity such as DNA secondary structure‐forming triplet repeat sequences relocalize to the NPC during DNA replication. Mutants that fail to reposition the triplet repeat locus to the (...) NPC cause repeat instability. Here, we review the types of DNA lesions that relocalize to the NPC, the putative mechanisms of relocalization, and the types of recombinational repair that are stimulated by the NPC, and present a model for NPC‐facilitated repair. (shrink)

DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling (...) methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children. DNA methylation, critical for embryo development, suffers significant changes after fertilization, including demethylation, remethylation and TET3-mediated oxidation of 5 mC to 5 hmC. In addition to infertility and environmental insults, ART could impact DNA methylation and ART related consequences in the offspring have been reported. (shrink)

Methylation of DNA plays an important role in the control of gene expression in higher eukaryotes. This is largely achieved by the packaging of methylated DNA into chromatin structures that are inaccessible to transcription factors and other proteins. Methylation involves the addition of a methyl group to the 5‐position of the cytosine base in DNA, a reaction catalysed by a DNA (cytosine‐5) methyltransferase. This reaction occurs in nuclear replication foci where the chromatin structure is loosened for replication, thereby allowing access (...) to methyltransferases. Partly as a result of their recognising the presence of a methylcytosine on the parental strand following replication, these large enzymes are able to maintain the distribution of methyl groups along the DNA of somatic cells and, thereby, maintain tissue‐specific patterns of gene expression. (shrink)

The pedagogical function of science teaching may benefit from an analysis of the historical-epistemic dimension, without neglecting the socio-political context in which a given research was carried out. In the case of DNA structure, the background of its discovery is particularly complex. Starting from the analysis of some papers, the view on the circumstances that led to their drafting broadens. We try to answer the fundamental question for any educator: why teach all that? Ethics issues are related to the general (...) organisation of research, increasingly focused on speed and competition. Even teaching is affected by these dynamics, not only in higher education, but also at secondary level; students should be made aware of this trend. The history of science could therefore favour a more general awareness. _SUNTO_ La funzione pedagogica dell’insegnamento scientifico può trarre vantaggio da un’analisi della dimensione storico-epistemica, senza trascurare il contesto socio-politico nel quale una determinata ricerca è stata condotta. Nel caso della struttura del DNA, i retroscena della sua scoperta sono particolarmente complessi. Dopo l’analisi di alcuni articoli, si allarga gradualmente la vista sulle circostanze che hanno condotto alla loro stesura. Si cerca di rispondere a una domanda fondamentale per ogni educatore: perché insegnare tutto ciò? Le questioni etiche riguardano l’organizzazione generale della ricerca, sempre più tesa alla velocità e alla competizione. Persino l’insegnamento è influenzato da dinamiche simili, non solo in ambito accademico, ma anche a livello secondario; gli studenti dovrebbero essere a conoscenza di questa tendenza. La storia della scienza può dunque favorire una maggiore consapevolezza. (shrink)

Recent studies based on next‐generation DNA sequencing have revealed that the female inactive X chromosome is replicated in a rapid, unorganized manner, and undergoes increased rates of mutation. These observations link the organization of DNA replication timing to gene regulation on one hand, and to the generation of mutations on the other hand. More generally, the exceptional biology of the inactive X chromosome highlights general principles of genome replication. Cells may control replication timing by a combination of intrinsic replication origin (...) properties, local chromatin states and global levels of replication factors, leading to a functional separation between the activity of genes and their mutation. (shrink)

This Christian sermon uses a DNA lab experience as a basis for theological reflection on ourselves and our offering. Who are we to God? What determines the self that we offer? Can the alphabet of DNA shed light for us on the Word of God in our lives? This first attempt to introduce the language and laboratory environment of genetic testing (represented by DNA fingerprinting) within a parish preaching context juxtaposes liturgical, scientific, and biblical language and settings for fresh insights.

Those objecting to human DNA patenting frequently do so on the grounds that the practice violates or threatens human dignity. For example, from 1993 to 1994, more than thirty organizations representing indigenous peoples approved formal declarations objecting to the National Institutes of Health's bid to patent viral DNA taken from subjects in Papua New Guinea and the Solomon Islands. Although these were not patents on human DNA, the organizations argued that the patents could harm and exploit indigenous peoples and violate (...) their cultural values. NIH eventually dropped one of its patent applications.On May 18, 1995, 180 religious leaders, led by biotechnology critic Jeremy Rifkin, held a press conference objecting to DNA patenting in Washington, D.C. In their “Joint Appeal against Human and Animal Patenting,” these leaders decried any attempt to patent nature. Some of the more outspoken members of the Joint Appeal likened DNA patenting to slavery, while others objected to treating human beings as marketable commodities. In his recent book, The Biotech Century, Rifkin rehashed the objections to DNA patenting voiced by members of the Joint Appeal. (shrink)

Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. Dissection (...) of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control. Torsional stress, and supercoiling generated by transcription, shape the topology of DNA. Furthermore, the resultant secondary DNA structures and their interacting partners provide feedback to regulate gene expression. Emerging evidence suggests these mechanisms, identified through analysis of the MYC promoter, are applicable genome-wide. (shrink)

The regulation of DNA replication is a fascinating biological problem both from a mechanistic angle—How is replication timing regulated?—and from an evolutionary one—Why is replication timing regulated? Recent work has provided significant insight into the first question. Detailed biochemical understanding of the mechanism and regulation of replication initiation has made possible robust hypotheses for how replication timing is regulated. Moreover, technical progress, including high‐throughput, single‐molecule mapping of replication initiation and single‐cell assays of replication timing, has allowed for direct testing of (...) these hypotheses in mammalian cells. This work has consolidated the conclusion that differential replication timing is a consequence of the varying probability of replication origin initiation. The second question is more difficult to directly address experimentally. Nonetheless, plausible hypotheses can be made and one—that replication timing contributes to the regulation of chromatin structure—has received new experimental support. (shrink)

DNA supercoiling is one of the mechanisms that can help unlinking of newly replicated DNA molecules. Although DNA topoisomerases, which catalyze the strand passing of DNA segments through one another, make the unlinking problem solvable in principle, it remains difficult to complete the process that enables the separation of the sister duplexes. A few different mechanisms were developed by nature to solve the problem. Some of the mechanisms are very intuitive while the others, like topology simplification by type II DNA (...) topoisomerases and DNA supercoiling, are not so evident. A computer simulation and analysis of linked sister plasmids formed inEscherichia colicells with suppressed topoisomerase IV suggests an insight into the latter mechanism. (shrink)

Abstract6‐methyladenine (6mA) is fairly abundant in nuclear DNA of basal fungi, ciliates and green algae. In these organisms, 6mA is maintained near transcription start sites in ApT context by a parental‐strand instruction dependent maintenance methyltransferase and is positively associated with transcription. In animals and plants, 6mA levels are high only in organellar DNA. The 6mA levels in nuclear DNA are very low. They are attributable to nucleotide salvage and the activity of otherwise mitochondrial METTL4, and may be considered as a (...) price that cells pay for adenine methylation in RNA and/or organellar DNA. Cells minimize this price by sanitizing dNTP pools to limit 6mA incorporation, and by converting 6mA that has been incorporated into DNA back to adenine. Hence, 6mA in nuclear DNA should be described as an epigenetic mark only in basal fungi, ciliates and green algae, but not in animals and plants. (shrink)

Science; Ethics; Politics; Beyond recombinant dna.

The aim of this paper is to explain the emergence and use of DNA fingerprinting technology in India, noting the specific concerns faced by the Indian Legal System related to the use of this novel forensic technology in the justice process. Furthermore, the proposed construction of a National DNA Data Bank is discussed taking into consideration the challenges faced by the government in legislating the DNA Bill into law. A critical analysis of the DNA Technology (Use and Application) Regulation Bill, (...) 2019 is provided to throw light upon many ethical, social, and legal issues that need to be addressed before the operationalization of the Bill to ensure that this technology is governed democratically to protect the civil liberties of citizens. (shrink)

DNA profiling is a well-established technology for use in the criminal justice system, both in courtrooms and elsewhere. The fact that DNA profiles are based on non-coding DNA and do not reveal details about the physical appearance of an individual has contributed to the acceptability of this type of evidence. Its success in criminal investigation, combined with major innovations in the field of genetics, have contributed to a change of role for this type of evidence. Nowadays DNA evidence is not (...) merely about identification, where trace evidence is compared to a sample taken from a suspect. An ever-growing role is anticipated for DNA profiling as an investigative tool, a technique aimed at generating a suspect where there is none. One of these applications is the inference of visible traits. As this article will show, racial classifications are at the heart of this application. The Netherlands and its legal regulation of 'externally visible traits' will serve as an example. It will be shown that, to make this technology work, a large number of actors has to be enrolled and their articulations invited. This indicates that instead of a 'silent witness', a DNA profile should rather be seen as an 'articulate collective'. Based on two cases, I argue that the normativity of visible traits is context-dependent. Taking into account the practices in which technology is put to use alerts us to novel ethical questions raised by their application. (shrink)

First the ‘Weismann barrier’ and later on Francis Crick’s ‘central dogma’ of molecular biology nourished the gene-centric paradigm of life, i.e., the conception of the gene/genome as a ‘central source’ from which hereditary specificity unidirectionally flows or radiates into cellular biochemistry and development. Today, due to advances in molecular genetics and epigenetics, such as the discovery of complex post-genomic and epigenetic processes in which genes are causally integrated, many theorists argue that a gene-centric conception of the organism has become problematic. (...) Here, we first explore the causal implications of the following two central dogma-related issues: (1) widespread reverse transcription—arguing for an extension from ‘DNA-genome’ to RNA-encompassing ‘NA-genome’ and, thus, from traditional DNA-centrism to a broader ‘NA-centrism’; and (2) the absence of a mechanism of reverse translation—arguing for the ‘structural primacy’ of NA-sequence over protein in cellular biochemistry. Secondly, we explore whether this latter conclusion can be extended to a ‘functional primacy’ of NA-sequence over protein in cellular biochemistry, which would imply a limited kind of ‘gene/NA-centrism’ confined to the subcellular level of NA/protein-based biochemistry. Finally, we explore the conditions—and their (non)fulfilment—for a more generalised form of gene-centrism extendable to higher levels of biological organisation. We conclude that the higher we go in the biological hierarchy, the more dubious gene-centric claims become. (shrink)

Over 30 million people worldwide have taken a commercial at-home DNA test, because they were interested in their genetic ancestry, disease predisposition or inherited traits. Yet, these consumer DNA data are also increasingly used for a very different purpose: to identify suspects in criminal investigations. By matching a suspect’s DNA with DNA from a suspect’s distant relatives who have taken a commercial at-home DNA test, law enforcement can zero in on a perpetrator. Such forensic use of consumer DNA data has (...) been performed in over 200 criminal investigations. However, this practice of so-called investigative genetic genealogy raises ethical concerns. In this paper, we aim to broaden the bioethical analysis on IGG by showing the limitations of an individual-based model. We discuss two concerns central in the debate: privacy and informed consent. However, we argue that IGG raises pressing ethical concerns that extend beyond these individual-focused issues. The very nature of the genetic information entails that relatives may also be affected by the individual customer’s choices. In this respect, we explore to what extent the ethical approach in the biomedical genetic context on consent and consequences for relatives can be helpful for the debate on IGG. We argue that an individual-based model has significant limitations in an IGG context. The ethical debate is further complicated by the international, transgenerational and commercial nature of IGG. We conclude that IGG should not only be approached as an individual but also—and perhaps primarily—as a collective issue. There are no data in this work. (shrink)

Eminent scientists are well-placed to bring the novel works of others, even if not in their own areas of expertise, to general attention. In so doing, they may be able to extend original accounts or introduce new terminologies, but they are basically messengers, not innovators. In the 1940s an evolutionary theory of biological aging was explained by Peter Medawar, and informational concepts relating to DNA were explained by Erwin Schrödinger. Both explanations were eventually traced back to the Victorian polymath Samuel (...) Butler—one by Medawar’s research associate Alex Comfort, and the other, albeit indirectly, by Schrödinger himself. In his time Butler’s works were too erudite for general readers and too laden with populist jargon for contemporary experts to take seriously. However, today it appears counterfactually plausible that an early acceptance of his ideas would have greatly quickened the pace of research. (shrink)

Genomic function is dictated by a combination of DNA sequence and the molecular mechanisms controlling access to genetic information. Access to DNA can be determined by the interpretation of covalent modifications that influence the packaging of DNA into chromatin, including DNA methylation and histone modifications. These modifications are believed to be forms of “epigenetic codes” that exist in discernable combinations that reflect cellular phenotype. Although DNA methylation is known to play important roles in gene regulation and genomic function, its contribution (...) to the encoding of epigenetic information is just beginning to emerge. Here we discuss paradigms associated with the various components of DNA methylation/demethylation and recent advances in the understanding of its dynamic regulation in the genome, integrating these mechanisms into a framework to explain how DNA methylation could contribute to epigenetic codes. (shrink)

The paper tries to show that an evolutionary perspective helps us to address what is called the adaptation problem, that is, the remarkable coherence, and seemingly successful design, existing between our cognitive tools and the phenomena of the material world. It argues that a fine-grained description of the structure and function of experimental techniques—as a special type amongst evolving scientific practices—is a condition for a better understanding and, ultimately, an explanation of how adaptation among the heterogeneous elements of experimental knowledge (...) is attained. Some apparently contradictory features of techniques, such as their high context-dependency and their capabilities to reproduce and diversify outside their original contexts, are addressed with the help of the concepts of technical variation and the historical entrenchment of phenomena in techniques. In order to do so, a case-study on the construction of satellite-DNA and the evolution of nucleic acid hybridization, a research project carried out by Roy J. Britten and his colleagues in the 1960s, is presented in detail. This case illustrates the close relationship existing between the evolution of techniques and the stabilization of phenomena in experimental biology. (shrink)

Recently, there has been a convergence of fields studying the processing of DNA, such as transcription, replication, and repair. This convergence has been centered around the packaging of DNA in chromatin. Chromatin structure affects all aspects of DNA processing because it modulates access of proteins to DNA. Therefore, a central theme has become the mechanism(s) for accessing DNA in chromatin. It seems likely that mechanisms involved in one of these processes may also be used in others. For example, the discovery (...) of transcriptional coactivators with histone acetyltransferase activity and chromatin remodeling complexes has provided possible mechanisms required for efficient repair of DNA in chromatin. BioEssays 21:596–603, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The repair of chromosomal double‐strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51‐mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms.

Phage DNA packaging occurs by DNA translocation into a prohead. Terminases are enzymes which initiate DNA packaging by cutting the DNA concatemer, and they are closely fitted structurally to the portal vertex of the prohead to form a ‘packasome’. Analysis among a number of phages supports an active role of the terminases in coupling ATP hydrolysis to DNA translocation through the portal. In phage T4 the small terminase subunit promotes a sequence‐specific terminase gene amplification within the chromosome. This link between (...) recombination and packaging suggests a DNA synapsis mechanism by the terminase to control packaging initiation, formally homologous to eukaryotic chromosome segregation. (shrink)

Type II DNA topoisomerase activity is required to change DNA topology. It is important in the relaxation of DNA supercoils generated by cellular processes, such as transcription and replication, and it is essential for the condensation of chromosomes and their segregation during mitosis. In mammals this activity is derived from at least two isoforms, termed DNA topoisomerase IIα and β. The α isoform is involved in chromosome condensation and segregation, whereas the role of the β isoform is not yet clear. (...) DNA topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the last 10 years. BioEssays 20:215–226, 1998.© 1998 John Wiley & Sons, Inc. (shrink)

Ancient DNA has been discovered in many types of preserved biological material, including bones, mummies, museum skins, insects in amber and plant fossils, and has become an important research tool in disciplines as diverse as archaeology, conservation biology and forensic science. In archaeology, ancient DNA can contribute both to the interpretation of individual sites and to the development of hypotheses about past populations. Site interpretation is aided by DNA‐based sex typing of fragmentary human bones, and by the use of genetic (...) techniques to assess the degree of kinship between the remains of different individuals. On a broader scale, population migrations can be traced by studying genetic markers in ancient DNA, as in recent studies of the colonisation of the Pacific islands, while ancient DNA in preserved plant remains can provide information on the development of agriculture. (shrink)

Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are direct (...) interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted. (shrink)

Definition of the problem:The frequency and scope of human genetic banking has increased significantly in recent years and is set to expand still further. Two of the major growth areas in medical research, pharmacogenomics and population genetics, rely on large DNA banks to provide extensive, centralised and standardised genetic information as well as clinical and personal data. This development raises ethical concerns. Arguments and conclusion: Our article focuses on the appropriateness of informed consent as a means to safeguard both research (...) subjects’ rights and their good will. It will be argued that information requirements are extensive, with regard to non-therapeutic research, feedback, type of consent and possible breaches of confidentiality as well as possible implications for third parties. Given the demand of these requirements and the danger that research facilitated by these huge DNA banks may not reflect public priorities, it is argued that the research needs be steered by trustees to ensure that the altruistic act of sample donation contributes to the public good. (shrink)

In this brief report, the authors argue that while a lot of concerns about forensic DNA databases have been raised using arguments from biomedical ethics, these databases are used in a complete different context from other biomedical tools. Because they are used in the struggle against crime, the decision to create or store a genetic profile cannot be left to the individual. Instead, this decision is made by officials of a society. These decisions have to be based on a policy (...) that is the concretisation of some of society's most fundamental ideas about its own nature and function. Individuals wanting to influence these decisions have to try to influence this policy, within the bounds of a state's own self-concept. This article is an attempt to reorient the discussion about forensic DNA databases from a biomedical debate to a more political–philosophical one. (shrink)

In his keynote address at a recent Intelligent Design (ID) conference at Biola University, ID leader William Dembski began by quoting "a well-known ID sympathizer" whom he had asked to assess the current state of the ID movement. Dembski explained that he had asked because, "after some initial enthusiasm on his part three years ago, his interest seemed to have flagged" (Dembski 2002). The sympathizer replied that..

In its last round of publications in September 2012, the Encyclopedia Of DNA Elements (ENCODE) assigned a biochemical function to most of the human genome, which was taken up by the media as meaning the end of ‘Junk DNA’. This provoked a heated reaction from evolutionary biologists, who among other things claimed that ENCODE adopted a wrong and much too inclusive notion of function, making its dismissal of junk DNA merely rhetorical. We argue that this criticism rests on misunderstandings concerning (...) the nature of the ENCODE project, the relevant notion of function and the claim that most of our genome is junk. We argue that evolutionary accounts of function presuppose functions as ‘causal roles’, and that selection is but a useful proxy for relevant functions, which might well be unsuitable to biomedical research. Taking a closer look at the discovery process in which ENCODE participates, we argue that ENCODE’s strategy of biochemical signatures successfully identified activities of DNA elements with an eye towards causal roles of interest to biomedical research. We argue that ENCODE’s controversial claim of functionality should be interpreted as saying that 80 % of the genome is engaging in relevant biochemical activities and is very likely to have a causal role in phenomena deemed relevant to biomedical research. Finally, we discuss ambiguities in the meaning of junk DNA and in one of the main arguments raised for its prevalence, and we evaluate the impact of ENCODE’s results on the claim that most of our genome is junk. (shrink)

Despite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a “barcode”, has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of taxa (...) have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool. BioEssays 29: 188–197, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Type II DNA topoisomerase activity is required to change DNA topology. It is important in the relaxation of DNA supercoils generated by cellular processes, such as transcription and replication, and it is essential for the condensation of chromosomes and their segregation during mitosis. In mammals this activity is derived from at least two isoforms, termed DNA topoisomerase IIα and β. The α isoform is involved in chromosome condensation and segregation, whereas the role of the β isoform is not yet clear. (...) DNA topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the last 10 years. BioEssays 20:215–226, 1998.© 1998 John Wiley & Sons, Inc. (shrink)

DNA methylation is a quintessential epigenetic mechanism. Widely considered a stable regulator of gene silencing, it represents a form of “molecular braille,” chemically printed on DNA to regulate its structure and the expression of genetic information. However, there was a time when methyl groups simply existed in cells, mysteriously speckled across the cytosine building blocks of DNA. Why was the code of life chemically modified, apparently by “no accident of enzyme action” (Wyatt 1951 )? If all cells in a body (...) share the same genome sequence, how do they adopt unique functions and maintain stable developmental states? Do cells remember? In this historical perspective, I review epigenetic history and principles and the tools, key scientists, and concepts that brought us the synthesis and discovery of prokaryotic and eukaryotic methylated DNA. Drawing heavily on Gerard Wyatt’s observation of asymmetric levels of methylated DNA across species, as well as to a pair of visionary 1975 DNA methylation papers, 5-methylcytosine is connected to DNA methylating enzymes in bacteria, the maintenance of stable cellular states over development, and to the regulation of gene expression through protein-DNA binding. These works have not only shaped our views on heritability and gene regulation but also remind us that core epigenetic concepts emerged from the intrinsic requirement for epigenetic mechanisms to exist. Driven by observations across prokaryotic and eukaryotic worlds, epigenetic systems function to access and interpret genetic information across all forms of life. Collectively, these works offer many guiding principles for our epigenetic understanding for today, and for the next generation of epigenetic inquiry in a postgenomics world. (shrink)

DNA joining enzymes play an essential role in the maintenance of genomic integrity and stability. Three mammalian genes encoding DNA ligases, LIG1, LIG3 and LIG4, have been identified. Since DNA ligase II appears to be derived from DNA ligase III by a proteolytic mechanism, the three LIG genes can account for the four biochemically distinct DNA ligase activities, DNA ligases I, II, III and IV, that have been purified from mammalian cell extracts. It is probable that the specific cellular roles (...) of these enzymes are determined by the proteins with which they interact. The specific involvement of DNA ligase I in DNA replication is mediated by the non‐catalytic amino‐terminal domain of this enzyme. Furthermore, DNA ligase I participates in DNA base excision repair as a component of a multiprotein complex. Two forms of DNA ligase III are produced by an alternative splicing mechanism. The ubiqitously expressed DNA ligase III‐α forms a complex with the DNA single‐strand break repair protein XRCC1. In contrast, DNA ligase III‐β, which does not interact with XRCC1, is only expressed in male meiotic germ cells, suggesting a role for this isoform in meiotic recombination. At present, there is very little information about the cellular functions of DNA ligase IV. (shrink)

As nation-states make greater efforts to regulate the flow of people on the move—refugees, economic migrants, and international travelers alike—advocates of DNA profiling technologies claim DNA testing provides a reliable and objective way of revealing a person’s true identity for immigration procedures. This article examines the use of DNA testing for family reunification in immigration cases in Finland, Germany, and the United States—the first transatlantic analysis of such cases—to explore the relationship between technology, the meaning of family, and immigration. Drawing (...) on our analyses of archival records, government documents, and interviews with immigration stakeholders, we argue that DNA testing is not conclusive about the meaning of family. While the technology may facilitate decision making for both would-be immigrants and state officials, our study shows hesitancy among the latter to let DNA testing make the final determination. We introduce the concept of social validity—whether the interpretation of test results matches social or political meanings in a given local context—in order to make sense of the complexities and challenges of DNA testing in practice. We show that DNA testing is not just a technology of belonging or a way to claim citizenship rights. It may also enable exclusion and denial of rights. (shrink)

Genes induced by the plant hormone auxin are probably involved in the execution of vital cellular functions and developmental processes. Experimental approaches designed to elucidate the molecular mechanisms of auxin action have focused on auxin perception, genetic dissection of the signaling apparatus and specific gene activation. Auxin‐responsive promoter elements of early genes provide molecular tools for probing auxin signaling in reverse. Functional analysis of several auxin‐specific promoters of unrelated early genes suggests combinatorial utilization of both conserved and variable elements. These (...) elements are arranged into autonomous domains and the combination of such modules generates uniquely composed promoters. Modular promoters allow for auxin‐mediated transcriptional responses to be revealed in a tissue‐ and development‐specific manner. (shrink)

While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue‐specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high‐resolution studies visualizing DNA replication patterns in the nucleus, and by allele‐specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously (...) thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non‐transcribed, “silent” chromatin. These observations alter current concepts about the regulation of DNA replication in non‐transcribed portions of the genome in general and in the inactive X‐chromosome in particular. (shrink)

The model of DNA-histones has the following elements: The hydrogen bonds between the complementary nucleotide bases function as informational gates. When the electrons π of one nucleotide base are excited, an exchange of protons is produced between the two complementary bases. The result is the displacement of the conjugated double bonds which facilitates the inter-molecular transmission of the electronic wave of excitation by electro-magnetic coupling. Each triplet of nucleotide bases of DNA fixes one definite amino acid . Between the nucleotide (...) bases and the amino acids there are constituted informational gates, which ensure the circulation of the electronic wave of excitation. An input signal molecule arrives at the receiver gene and unleashes the activity of the enzymes which introduce in the DNA-histones system the electronic wave of excitation. The electronic wave of excitation arises as a result of the break of the high-energy bonds of ATP. Then, the electronic excitation is transmitted to the productor gene where it represents the signal for starting the synthesis of the mRNA.Le modèle de système ADN-Histone a les éléments suivants: Les liaisons d'hydrogène entre les bases nucléotidiques complémentaires fonctionnent comme des portes informationnelles. Quand les électrons π d'une base nucléotidique sont excités, il se produit un échange de protons entre les bases complémentaires. Le résultat est un déplacement des doubles liaisons conjugées qui facilite la transmission de l'onde d'excitation électronique par un couplage électromagnétique. Chaque triplet de bases nucléotidiques de l'ADN fixe un certain amino-acide . Entre les bases nucléodiques et les amino-acides se constituent des portes informationnelles qui assurent la circulation de l'onde d'excitation dlectronique. Une molécule signal d'entrée arrive au gène récepteur et déclenche l'activité des enzymes qui introduisent dans le système ADN-histone l'excitation électronique. L'excitation électronique apparait comme résultat de la rupture des liaisons de haute énergie del' ATP. l'Onde d'excitation électronique est transmise au gène producteur, où elle rdprésente le signal pour faire commencer la synthèse de l'ARNm.Das Modell des DNS-Histonen Systems weist folgende Elemente auf: Die Wasserstoffbindungen zwischen den komplementäaren Nukleotidbasen funktionieren wie informationale Pforten. Wenn die π Elektronen einer Nukleotidbase erregt werden, ensteht ein Protonenwechsel zwischen den Komplementären Basen. Das Ergebnis ist eine Verschiebung der konjugierten Doppelbindungen, die die Weiterleitung der elektronischen Erregungswelle durch eine elektromagnetische Kupplung erleichtert. Jedes Nukleotidbasentriplett der DNS fixiert eine bestimmte Aminosäure . Zwischen den Nukelotidbasen und den Aminosäuren entstehen Informationspforten, welche den Umlauf der elektronischen Erregungswelle sichern. Ein Eintrittsignal Moleküul gelangt zur Rezeptorgen und löst die Aktivität von Enzymen aus, welche die elektronische Erregungswelle in das DNS-Histonen System einführen werden. Die elektronische Erregungswelle erscheint als Ergebnis der Spaltung der hochenergetischen Bindungen des ATP-s. Die elektronische Erregungswelle wird alsdann zur Produktorgen weitergeleitet, wo sie das Signal zum Beginn der Synthese der mRNS darstellt. (shrink)