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Virology Oct 2014Genome encapsidation is an essential step in the life cycle of viruses. Viruses either use some of the most powerful ATP-dependent motors to compel the genetic material... (Review)
Review
Genome encapsidation is an essential step in the life cycle of viruses. Viruses either use some of the most powerful ATP-dependent motors to compel the genetic material into the preformed capsid or make use of the positively charged proteins to bind and condense the negatively charged genome in an energy-independent manner. While the former is a hallmark of large DNA viruses, the latter is commonly seen in small DNA and RNA viruses. Discoveries of many complex giant viruses such as mimivirus, megavirus, pandoravirus, etc., belonging to the nucleo-cytoplasmic large DNA virus (NCLDV) superfamily have changed the perception of genome packaging in viruses. From what little we have understood so far, it seems that the genome packaging mechanism in NCLDVs has nothing in common with other well-characterized viral packaging systems such as the portal-terminase system or the energy-independent system. Recent findings suggest that in giant viruses, the genome segregation and packaging processes are more intricately coupled than those of other viral systems. Interestingly, giant viral packaging systems also seem to possess features that are analogous to bacterial and archaeal chromosome segregation. Although there is a lot of diversity in terms of host range, type of genome, and genome size among viruses, they all seem to use three major types of independent innovations to accomplish genome encapsidation. Here, we have made an attempt to comprehensively review all the known viral genome packaging systems, including the one that is operative in giant viruses, by proposing a simple and expanded classification system that divides the viral packaging systems into three large groups (types I-III) on the basis of the mechanism employed and the relatedness of the major packaging proteins. Known variants within each group have been further classified into subgroups to reflect their unique adaptations.
Topics: DNA Packaging; DNA Viruses; DNA, Viral; Genome, Viral; Models, Biological; Virus Assembly
PubMed: 24998349
DOI: 10.1016/j.virol.2014.06.022 -
DNA Repair Dec 2015Base Excision Repair (BER) is a conserved, intracellular DNA repair system that recognizes and removes chemically modified bases to insure genomic integrity and prevent... (Review)
Review
Base Excision Repair (BER) is a conserved, intracellular DNA repair system that recognizes and removes chemically modified bases to insure genomic integrity and prevent mutagenesis. Aberrant BER has been tightly linked with a broad spectrum of human pathologies, such as several types of cancer, neurological degeneration, developmental abnormalities, immune dysfunction and aging. In the cell, BER must recognize and remove DNA lesions from the tightly condensed, protein-coated chromatin. Because chromatin is necessarily refractory to DNA metabolic processes, like transcription and replication, the compaction of the genomic material is also inhibitory to the repair systems necessary for its upkeep. Multiple ATP-dependent chromatin remodelling (ACR) complexes play essential roles in modulating the protein-DNA interactions within chromatin, regulating transcription and promoting activities of some DNA repair systems, including double-strand break repair and nucleotide excision repair. However, it remains unclear how BER operates in the context of chromatin, and if the chromatin remodelling processes that govern transcription and replication also actively regulate the efficiency of BER. In this review we highlight the emerging role of ACR in regulation of BER.
Topics: Chromatin Assembly and Disassembly; DNA; DNA Repair; Humans
PubMed: 26422134
DOI: 10.1016/j.dnarep.2015.09.011 -
Biochimica Et Biophysica Acta.... Dec 2022The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical... (Review)
Review
The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical innovations in next generation sequencing. RNA interference, histone modification, DNA methylation and chromatin remodelling are epigenetic processes that control gene expression without causing mutations in the DNA. Although epigenetic abnormalities are thought to be a symptom of cell tumorigenesis and malignant events that impact tumor growth and drug resistance, physicians believe that related processes might be a key therapeutic target for cancer treatment and prevention due to the reversible nature of these processes. A plethora of novel strategies for addressing epigenetics in cancer therapy for immuno-oncological complications are currently available - ranging from basic treatment to epigenetic editing. - and they will be the subject of this comprehensive review. In this review, we cover most of the advancements made in the field of targeting epigenetics with special emphasis on microbiology, plasma science, biophysics, pharmacology, molecular biology, phytochemistry, and nanoscience.
Topics: Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; Neoplasms
PubMed: 36126898
DOI: 10.1016/j.bbadis.2022.166552 -
Structure (London, England : 1993) Apr 2022Bacteriophage lambda is an excellent model system for studying capsid assembly of double-stranded DNA (dsDNA) bacteriophages, some dsDNA archaeal viruses, and...
Bacteriophage lambda is an excellent model system for studying capsid assembly of double-stranded DNA (dsDNA) bacteriophages, some dsDNA archaeal viruses, and herpesviruses. HK97 fold coat proteins initially assemble into a precursor capsid (procapsid) and subsequent genome packaging triggers morphological expansion of the shell. An auxiliary protein is required to stabilize the expanded capsid structure. To investigate the capsid maturation mechanism, we determined the cryo-electron microscopy structures of the bacteriophage lambda procapsid and mature capsid at 3.88 Å and 3.76 Å resolution, respectively. Besides primarily rigid body movements of common features of the major capsid protein gpE, large-scale structural rearrangements of other domains occur simultaneously. Assembly of intercapsomers within the procapsid is facilitated by layer-stacking effects at 3-fold vertices. Upon conformational expansion of the capsid shell, the missing top layer is fulfilled by cementing the gpD protein against the internal pressure of DNA packaging. Our structures illuminate the assembly mechanisms of dsDNA viruses.
Topics: Bacteriophage lambda; Capsid; Capsid Proteins; Cryoelectron Microscopy; DNA Packaging; Virus Assembly
PubMed: 35026161
DOI: 10.1016/j.str.2021.12.009 -
ACS Chemical Biology Mar 2022The formation of chromatin not only compacts the eukaryotic genome into the nucleus but also provides a mechanism for the regulation of all DNA templated processes.... (Review)
Review
The formation of chromatin not only compacts the eukaryotic genome into the nucleus but also provides a mechanism for the regulation of all DNA templated processes. Spatial and temporal modulation of the chromatin structure is critical in such regulation and involves fine-tuned functioning of the basic subunit of chromatin, the nucleosome. It has become apparent that the nucleosome is an inherently dynamic system, but characterization of these dynamics at the atomic level has remained challenging. NMR spectroscopy is a powerful tool for investigating the conformational ensemble and dynamics of proteins and protein complexes, and recent advances have made the study of large systems possible. Here, we review recent studies which utilize NMR spectroscopy to uncover the atomic level conformation and dynamics of the nucleosome and provide a better understanding of the importance of these dynamics in key regulatory events.
Topics: Chromatin; Chromatin Assembly and Disassembly; Magnetic Resonance Spectroscopy; Molecular Conformation; Nucleosomes
PubMed: 35196453
DOI: 10.1021/acschembio.1c00954 -
Molecular Oncology Aug 2011The integrity of the human genome is constantly threatened by genotoxic agents that cause DNA damage. Inefficient or inaccurate repair of DNA lesions triggers genome... (Review)
Review
The integrity of the human genome is constantly threatened by genotoxic agents that cause DNA damage. Inefficient or inaccurate repair of DNA lesions triggers genome instability and can lead to cancer development or even cell death. Cells counteract the adverse effects of DNA lesions by activating the DNA damage response (DDR), which entails a coordinated series of events that regulates cell cycle progression and repair of DNA lesions. Efficient DNA repair in living cells is complicated by the packaging of genomic DNA into a condensed, often inaccessible structure called chromatin. Cells utilize post-translational histone modifications and ATP-dependent chromatin remodeling to modulate chromatin structure and increase the accessibility of the repair machinery to lesions embedded in chromatin. Here we review and discuss our current knowledge and recent advances on DNA damage-induced chromatin changes and their implications for the mammalian DNA damage response, genome stability and carcinogenesis. Exploiting our improving understanding of how modulators of chromatin structure orchestrate the DDR may provide new avenues to improve cancer management.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; DNA Damage; DNA Repair; Histones; Humans; Neoplasms; Protein Processing, Post-Translational
PubMed: 21782533
DOI: 10.1016/j.molonc.2011.06.001 -
Protein & Cell May 2020
Topics: Bacteriophages; DNA Packaging; DNA, Viral; Models, Molecular
PubMed: 32266588
DOI: 10.1007/s13238-020-00715-9 -
International Journal of Molecular... Feb 2024Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often represents the evolution of pathological conditions,... (Review)
Review
Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often represents the evolution of pathological conditions, causes organ failure, and can, in extreme cases, compromise the functionality of organs to the point of causing death. In recent years, considerable efforts have been made to understand the molecular mechanisms underlying fibrotic evolution and to identify possible therapeutic strategies. Great interest has been aroused by the discovery of a molecular association between epithelial to mesenchymal plasticity (EMP), in particular epithelial to mesenchymal transition (EMT), and fibrogenesis, which has led to the identification of complex molecular mechanisms closely interconnected with each other, which could explain EMT-dependent fibrosis. However, the result remains unsatisfactory from a therapeutic point of view. In recent years, advances in epigenetics, based on chromatin remodeling through various histone modifications or through the intervention of non-coding RNAs (ncRNAs), have provided more information on the fibrotic process, and this could represent a promising path forward for the identification of innovative therapeutic strategies for organ fibrosis. In this review, we summarize current research on epigenetic mechanisms involved in organ fibrosis, with a focus on epigenetic regulation of EMP/EMT-dependent fibrosis.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Epithelial-Mesenchymal Transition; Fibrosis; Chromatin Assembly and Disassembly
PubMed: 38474021
DOI: 10.3390/ijms25052775 -
FEBS Letters Aug 2014X-chromosome inactivation represents an epigenetics paradigm and a powerful model system of facultative heterochromatin formation triggered by a non-coding RNA, Xist,... (Review)
Review
X-chromosome inactivation represents an epigenetics paradigm and a powerful model system of facultative heterochromatin formation triggered by a non-coding RNA, Xist, during development. Once established, the inactive state of the Xi is highly stable in somatic cells, thanks to a combination of chromatin associated proteins, DNA methylation and nuclear organization. However, sporadic reactivation of X-linked genes has been reported during ageing and in transformed cells and disappearance of the Barr body is frequently observed in cancer cells. In this review we summarise current knowledge on the epigenetic changes that accompany X inactivation and discuss the extent to which the inactive X chromosome may be epigenetically or genetically perturbed in breast cancer.
Topics: Animals; Chromatin Assembly and Disassembly; Embryonic Development; Humans; Neoplasms; X Chromosome Inactivation
PubMed: 24937141
DOI: 10.1016/j.febslet.2014.06.023 -
Viruses Mar 2019Herpesvirus infection is an orderly, regulated process. Among these viruses, the encapsidation of viral DNA is a noteworthy link; the entire process requires a powered... (Review)
Review
Herpesvirus infection is an orderly, regulated process. Among these viruses, the encapsidation of viral DNA is a noteworthy link; the entire process requires a powered motor that binds to viral DNA and carries it into the preformed capsid. Studies have shown that this power motor is a complex composed of a large subunit, a small subunit, and a third subunit, which are collectively known as terminase. The terminase large subunit is highly conserved in herpesvirus. It mainly includes two domains: the C-terminal nuclease domain, which cuts the viral concatemeric DNA into a monomeric genome, and the N-terminal ATPase domain, which hydrolyzes ATP to provide energy for the genome cutting and transfer activities. Because this process is not present in eukaryotic cells, it provides a reliable theoretical basis for the development of safe and effective anti-herpesvirus drugs. This article reviews the genetic characteristics, protein structure, and function of the herpesvirus terminase large subunit, as well as the antiviral drugs that target the terminase large subunit. We hope to provide a theoretical basis for the prevention and treatment of herpesvirus.
Topics: DNA Packaging; DNA, Viral; Drug Development; Endodeoxyribonucleases; Herpesviridae; Herpesviridae Infections; Models, Molecular; Protein Domains; Protein Subunits; Viral Proteins; Virus Assembly
PubMed: 30841485
DOI: 10.3390/v11030219