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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 polymerase --- DNA polymerase evolution --- DNA polymerase fidelity --- DNA sequencing --- molecular diagnostics --- next generation sequencing --- PCR --- PCR inhibitors

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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.

DNA replication --- DNA repair --- genomic instability --- replication checkpoint --- telomere replication --- replisome --- replication stress --- DNA polymerase --- DNA helicase --- translesion synthesis --- cancer

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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.

DNA Damage --- DNA Repair --- DNA damage response --- genome instability --- Genome integrity

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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.

RNA-dependent DNA polymerase --- retrotransposon --- reverse transcriptase --- Mobile DNA --- genome stability --- cellular differentiation --- model organisms --- transposon --- DNA repair

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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.

Forensic DNA profiling --- interpretation --- Statistics and the law --- probability theory --- Commercialization --- DNA transfer --- Low-template DNA analysis --- forensic molecular biology --- Bacterial DNA