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The FEBS Journal Jun 2015The proposal of a double-helical structure for DNA over 60 years ago provided an eminently satisfying explanation for the heritability of genetic information. But why is... (Review)
Review
The proposal of a double-helical structure for DNA over 60 years ago provided an eminently satisfying explanation for the heritability of genetic information. But why is DNA, and not RNA, now the dominant biological information store? We argue that, in addition to its coding function, the ability of DNA, unlike RNA, to adopt a B-DNA structure confers advantages both for information accessibility and for packaging. The information encoded by DNA is both digital - the precise base specifying, for example, amino acid sequences - and analogue. The latter determines the sequence-dependent physicochemical properties of DNA, for example, its stiffness and susceptibility to strand separation. Most importantly, DNA chirality enables the formation of supercoiling under torsional stress. We review recent evidence suggesting that DNA supercoiling, particularly that generated by DNA translocases, is a major driver of gene regulation and patterns of chromosomal gene organization, and in its guise as a promoter of DNA packaging enables DNA to act as an energy store to facilitate the passage of translocating enzymes such as RNA polymerase.
Topics: Animals; Chromatin Assembly and Disassembly; DNA; DNA, Superhelical; Energy Metabolism; Genetic Phenomena; Genetics; Genome; History, 20th Century; History, 21st Century; Humans; Nucleic Acid Conformation
PubMed: 25903461
DOI: 10.1111/febs.13307 -
Cold Spring Harbor Perspectives in... Sep 2013Poxviruses are large, enveloped viruses that replicate in the cytoplasm and encode proteins for DNA replication and gene expression. Hairpin ends link the two strands of... (Review)
Review
Poxviruses are large, enveloped viruses that replicate in the cytoplasm and encode proteins for DNA replication and gene expression. Hairpin ends link the two strands of the linear, double-stranded DNA genome. Viral proteins involved in DNA synthesis include a 117-kDa polymerase, a helicase-primase, a uracil DNA glycosylase, a processivity factor, a single-stranded DNA-binding protein, a protein kinase, and a DNA ligase. A viral FEN1 family protein participates in double-strand break repair. The DNA is replicated as long concatemers that are resolved by a viral Holliday junction endonuclease.
Topics: DNA Packaging; DNA Replication; DNA, Viral; DNA-Binding Proteins; Genome, Viral; Models, Biological; Poxviridae
PubMed: 23838441
DOI: 10.1101/cshperspect.a010199 -
Nature Reviews. Molecular Cell Biology Oct 2017Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of... (Review)
Review
Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers. Understanding the role of PARP1 in maintaining genome integrity is not only important for the design of novel chemotherapeutic agents, but is also crucial for gaining insights into the mechanisms of chemoresistance in cancer cells. In this Review, we discuss the roles of PARP1 in mediating various aspects of DNA metabolism, such as single-strand break repair, nucleotide excision repair, double-strand break repair and the stabilization of replication forks, and in modulating chromatin structure.
Topics: Animals; Chromatin Assembly and Disassembly; DNA Damage; DNA Repair; DNA Replication; Humans; Poly (ADP-Ribose) Polymerase-1
PubMed: 28676700
DOI: 10.1038/nrm.2017.53 -
Molecular Aspects of Medicine 2013While the eukaryotic genome is the same throughout all somatic cells in an organism, there are specific structures and functions that discern one type of cell from... (Review)
Review
While the eukaryotic genome is the same throughout all somatic cells in an organism, there are specific structures and functions that discern one type of cell from another. These differences are due to the cell's unique gene expression patterns that are determined during cellular differentiation. Interestingly, these cell-specific gene expression patterns can be affected by an organism's environment throughout its lifetime leading to phenotypical changes that have the potential of altering risk of some diseases. Both cell-specific gene expression signatures and environment mediated changes in expression patterns can be explained by a complex network of modifications to the DNA, histone proteins and degree of DNA packaging called epigenetic marks. Several areas of research have formed to study these epigenetic modifications, including DNA methylation, histone modifications, chromatin remodeling and microRNA (miRNA). The original definition of epigenetics incorporates inheritable but reversible phenomena that affect gene expression without altering base pairs. Even though not all of the above listed epigenetic traits have demonstrated heritability, they can all alter gene transcription without modification to the underlying genetic sequence. Because these epigenetic patterns can also be affected by an organism's environment, they serve as an important bridge between life experiences and phenotypes. Epigenetic patterns may change throughout one's lifespan, by an early life experience, environmental exposure or nutritional status. Epigenetic signatures influenced by the environment may determine our appearance, behavior, stress response, disease susceptibility, and even longevity. The interaction between types of epigenetic modifications in response to environmental factors and how environmental cues affect epigenetic patterns will further elucidate how gene transcription can be affectively altered.
Topics: Animals; Chromatin Assembly and Disassembly; DNA Methylation; DNA-Binding Proteins; Epigenesis, Genetic; Epigenomics; Gene-Environment Interaction; Histones; Humans; MicroRNAs; Protein Processing, Post-Translational; RNA Interference; Transcription, Genetic
PubMed: 22906839
DOI: 10.1016/j.mam.2012.07.018 -
Nature Reviews. Molecular Cell Biology Jul 2017Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that... (Review)
Review
Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase-translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation. We propose the 'hourglass' model of remodeller function, in which each remodeller subfamily utilizes diverse specialized proteins and protein domains to assist in nucleosome targeting or to differentially detect nucleosome epitopes. These modules converge to regulate a common DNA translocation mechanism, to inform the conserved ATPase 'motor' on whether and how to apply DNA translocation, which together achieve the various outcomes of chromatin remodelling: nucleosome assembly, chromatin access and nucleosome editing.
Topics: Adenosine Triphosphate; Animals; Chromatin Assembly and Disassembly; DNA; Humans; Nucleosomes
PubMed: 28512350
DOI: 10.1038/nrm.2017.26 -
Microbiological Research 2018Bacteriophage particles are the most abundant biological entities on our planet, infecting specific bacterial hosts in every known environment and being major drivers of... (Review)
Review
Bacteriophage particles are the most abundant biological entities on our planet, infecting specific bacterial hosts in every known environment and being major drivers of bacterial adaptive evolution. The study of bacteriophage particles potentially sheds light on the development of new biotechnology products. Bacteriophage therapy, although not new, makes use of strictly lytic phage particles as an alternative in the antimicrobial treatment of resistant bacterial infections and is being rediscovered as a safe method due to the fact that these biological entities devoid of any metabolic machinery do not have affinity to eukaryotic cells. Furthermore, bacteriophage-based vaccination is emerging as one of the most promising preventive strategies. This review paper discusses the biological nature of bacteriophage particles, their mode(s) of action and potential exploitation in modern biotechnology. Topics covered in detail include the potential of bacteriophage particles in human infections (bacteriophage therapy), nanocages for gene delivery, food biopreservation and safety, biocontrol of plant pathogens, phage display, bacterial biosensing devices, vaccines and vaccine carriers, biofilm and bacterial growth control, surface disinfection, corrosion control, together with structural and functional stabilization issues.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Biofilms; Biological Control Agents; Biosensing Techniques; Biotechnology; Corrosion; DNA Packaging; Dental Caries; Disinfection; Food Preservation; Food Safety; Gene Transfer Techniques; Humans; Nanostructures; Phage Therapy; Vaccination; Vaccines
PubMed: 29853167
DOI: 10.1016/j.micres.2018.04.007 -
Essays in Biochemistry Apr 2019This collection of reviews focuses on the most exciting areas of DNA packaging at the current time. Many of the new discoveries are driven by the development of...
This collection of reviews focuses on the most exciting areas of DNA packaging at the current time. Many of the new discoveries are driven by the development of molecular or imaging techniques, and these are providing insights into the complex world of chromatin. As these new techniques continue to improve, we will be able to answer many of the questions we have now, while likely raising many new ones.
Topics: Animals; DNA; DNA Packaging; Histones; Nucleosomes; RNA
PubMed: 31015379
DOI: 10.1042/EBC20190040 -
Cold Spring Harbor Perspectives in... Jul 2021Immediately following the discovery of the structure of DNA and the semi-conservative replication of the parental DNA sequence into two new DNA strands, it became... (Review)
Review
Immediately following the discovery of the structure of DNA and the semi-conservative replication of the parental DNA sequence into two new DNA strands, it became apparent that DNA replication is organized in a temporal and spatial fashion during the S phase of the cell cycle, correlated with the large-scale organization of chromatin in the nucleus. After many decades of limited progress, technological advances in genomics, genome engineering, and imaging have finally positioned the field to tackle mechanisms underpinning the temporal and spatial regulation of DNA replication and the causal relationships between DNA replication and other features of large-scale chromosome structure and function. In this review, we discuss these major recent discoveries as well as expectations for the coming decade.
Topics: Animals; DNA Packaging; DNA Replication Timing; Genome; Humans; Mammals
PubMed: 33558366
DOI: 10.1101/cshperspect.a040162 -
Advances in Anatomy, Embryology, and... 2017Herpes simplex virus type I (HSV-1) is the causative agent of several pathologies ranging in severity from the common cold sore to life-threatening encephalitic... (Review)
Review
Herpes simplex virus type I (HSV-1) is the causative agent of several pathologies ranging in severity from the common cold sore to life-threatening encephalitic infection. During productive lytic infection, over 80 viral proteins are expressed in a highly regulated manner, resulting in the replication of viral genomes and assembly of progeny virions. The virion of all herpesviruses consists of an external membrane envelope, a proteinaceous layer called the tegument, and an icosahedral capsid containing the double-stranded linear DNA genome. The capsid shell of HSV-1 is built from four structural proteins: a major capsid protein, VP5, which forms the capsomers (hexons and pentons), the triplex consisting of VP19C and VP23 found between the capsomers, and VP26 which binds to VP5 on hexons but not pentons. In addition, the dodecameric pUL6 portal complex occupies 1 of the 12 capsid vertices, and the capsid vertex specific component (CVSC), a heterotrimer complex of pUL17, pUL25, and pUL36, binds specifically to the triplexes adjacent to each penton. The capsid is assembled in the nucleus where the viral genome is packaged into newly assembled closed capsid shells. Cleavage and packaging of replicated, concatemeric viral DNA requires the seven viral proteins encoded by the UL6, UL15, UL17, UL25, UL28, UL32, and UL33 genes. Considerable advances have been made in understanding the structure of the herpesvirus capsid and the function of several of the DNA packaging proteins by applying biochemical, genetic, and structural techniques. This review is a summary of recent advances with respect to the structure of the HSV-1 virion capsid and what is known about the function of the seven packaging proteins and their interactions with each other and with the capsid shell.
Topics: Animals; Capsid; DNA Packaging; Herpesviridae; Humans; Viral Proteins; Virion; Virus Assembly
PubMed: 28528442
DOI: 10.1007/978-3-319-53168-7_6 -
Cold Spring Harbor Perspectives in... May 2021Genomic information is encoded on long strands of DNA, which are folded into chromatin and stored in a tiny nucleus. Nuclear chromatin is a negatively charged polymer... (Review)
Review
Genomic information is encoded on long strands of DNA, which are folded into chromatin and stored in a tiny nucleus. Nuclear chromatin is a negatively charged polymer composed of DNA, histones, and various nonhistone proteins. Because of its highly charged nature, chromatin structure varies greatly depending on the surrounding environment (e.g., cations, molecular crowding, etc.). New technologies to capture chromatin in living cells have been developed over the past 10 years. Our view on chromatin organization has drastically shifted from a regular and static one to a more variable and dynamic one. Chromatin forms numerous compact dynamic domains that act as functional units of the genome in higher eukaryotic cells and locally appear liquid-like. By changing DNA accessibility, these domains can govern various functions. Based on new evidences from versatile genomics and advanced imaging studies, we discuss the physical nature of chromatin in the crowded nuclear environment and how it is regulated.
Topics: Animals; Cell Nucleus; Chromatin; DNA Packaging; Genome; Humans; Molecular Conformation
PubMed: 33820775
DOI: 10.1101/cshperspect.a040675