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Experimental Hematology Oct 2016Understanding transformation mechanisms other than genetic aberrations has recently captured the attention of cancer researchers. To date, the role of transposable... (Review)
Review
Understanding transformation mechanisms other than genetic aberrations has recently captured the attention of cancer researchers. To date, the role of transposable elements (TEs) in tumor development remains largely undefined. However, an increasing number of studies have reported that loss of epigenetic control causes TE reactivation and consequent oncogenic transcription. Here, we discuss principal examples of TEs-driven oncogenesis. Available data suggest that long terminal repeats and long interspersed nuclear elements play a pivotal role as alternative promoters. These findings provide definitive experimental evidence that repetitive elements are a powerful underestimated force toward oncogenesis and open the possibility to new therapeutic treatments.
Topics: Animals; Cell Transformation, Neoplastic; DNA Transposable Elements; Epigenesis, Genetic; Humans; Long Interspersed Nucleotide Elements; Neoplasms; Promoter Regions, Genetic; Terminal Repeat Sequences
PubMed: 27377925
DOI: 10.1016/j.exphem.2016.06.251 -
Nucleic Acids Research Aug 2021Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein...
Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein production, creation of transgenic animals, and engineering cell and gene therapy products. The piggyBac transposon family includes transposase or transposase-like proteins from a variety of species including insect, bat and human. Recently, human piggyBac transposable element derived 5 (PGBD5) protein was reported to be able to transpose piggyBac transposons in human cells raising possible safety concerns for piggyBac-mediated gene transfer applications. We evaluated three piggyBac-like proteins across species including piggyBac (insect), piggyBat (bat) and PGBD5 (human) for their ability to mobilize piggyBac transposons in human cells. We observed a lack of cross-species transposition activity. piggyBac and piggyBat activity was restricted to their cognate transposons. PGBD5 was unable to mobilize piggyBac transposons based on excision, colony count and plasmid rescue analysis, and it was unable to bind piggyBac terminal repeats. Within the piggyBac family, we observed a lack of cross-species activity and found that PGBD5 was unable to bind, excise or integrate piggyBac transposons in human cells. Transposition activity appears restricted within species within the piggyBac family of mobile genetic elements.
Topics: Animals; Cell Line; DNA Transposable Elements; Genetic Vectors; Humans; Interspersed Repetitive Sequences; Mutagenesis, Insertional; Plasmids; Transcription Factors; Transposases
PubMed: 34232995
DOI: 10.1093/nar/gkab578 -
Genes Feb 2020Cas3 has essential functions in CRISPR immunity but its other activities and roles, in vitro and in cells, are less widely known. We offer a concise review of the latest... (Review)
Review
Cas3 has essential functions in CRISPR immunity but its other activities and roles, in vitro and in cells, are less widely known. We offer a concise review of the latest understanding and questions arising from studies of Cas3 mechanism during CRISPR immunity, and highlight recent attempts at using Cas3 for genetic editing. We then spotlight involvement of Cas3 in other aspects of cell biology, for which understanding is lacking-these focus on CRISPR systems as regulators of cellular processes in addition to defense against mobile genetic elements.
Topics: Clustered Regularly Interspaced Short Palindromic Repeats; DNA Helicases; Gene Editing; Interspersed Repetitive Sequences; Models, Molecular; Protein Conformation
PubMed: 32085454
DOI: 10.3390/genes11020208 -
Current Opinion in Microbiology Jun 2017Clustered, regularly interspaced, short, palindromic repeats (CRISPR) loci, together with their CRISPR-associated (Cas) proteins, provide bacteria and archaea with... (Review)
Review
Clustered, regularly interspaced, short, palindromic repeats (CRISPR) loci, together with their CRISPR-associated (Cas) proteins, provide bacteria and archaea with adaptive immunity against invasion by bacteriophages, plasmids, and other mobile genetic elements. These host defenses impart selective pressure on phages and mobile elements to evolve countermeasures against CRISPR immunity. As a consequence of this pressure, phages and mobile elements have evolved 'anti-CRISPR' proteins that function as direct inhibitors of diverse CRISPR-Cas effector complexes. Some of these CRISPR-Cas complexes can be deployed as genome engineering platforms, and anti-CRISPRs could therefore be useful in exerting spatial, temporal, or conditional control over genome editing and related applications. Here we describe the discovery of anti-CRISPRs, the range of CRISPR-Cas systems that they inhibit, their mechanisms of action, and their potential utility in biotechnology.
Topics: Bacteria; Bacteriophages; CRISPR-Cas Systems; Evolution, Molecular; Host-Parasite Interactions; Interspersed Repetitive Sequences
PubMed: 28668720
DOI: 10.1016/j.mib.2017.06.003 -
Psychiatria Danubina Dec 2009Variation in the human genome may explain genetic contributions to complex traits and common diseases. (Review)
Review
OBJECTIVES
Variation in the human genome may explain genetic contributions to complex traits and common diseases.
FINDINGS
Until recently, single nucleotide polymorphisms were thought to be the most prevalent form of interindividual genetic variation. However, structural genomic rearrangements such as deletions, duplications, and inversions lead to variation in gene copy number and contribute even more to genomic diversity. Other sources of genomic variation include noncoding genes, pseudogenes, and mobile genetic elements (transposons).
CONCLUSIONS
Genome dynamics, including changes in gene number and position as well as epigenetic modifications of coding and noncoding sequences, can affect regulation of gene expression and may contribute to the variability of complex phenotypes.
Topics: Chromosome Deletion; Chromosome Inversion; DNA Copy Number Variations; DNA Transposable Elements; Epigenesis, Genetic; Gene Duplication; Gene Expression Regulation; Genetic Variation; Genome, Human; Genomic Structural Variation; Humans; Interspersed Repetitive Sequences; Introns; Mental Disorders; Phenotype; Polymorphism, Single Nucleotide; Pseudogenes; RNA, Untranslated
PubMed: 19935494
DOI: No ID Found -
Cell Reports Jul 2023Prokaryotic adaptation is strongly influenced by the horizontal acquisition of beneficial traits via mobile genetic elements (MGEs), such as viruses/bacteriophages and... (Review)
Review
Prokaryotic adaptation is strongly influenced by the horizontal acquisition of beneficial traits via mobile genetic elements (MGEs), such as viruses/bacteriophages and plasmids. However, MGEs can also impose a fitness cost due to their often parasitic nature and differing evolutionary trajectories. In response, prokaryotes have evolved diverse immune mechanisms against MGEs. Recently, our understanding of the abundance and diversity of prokaryotic immune systems has greatly expanded. These defense systems can degrade the invading genetic material, inhibit genome replication, or trigger abortive infection, leading to population protection. In this review, we highlight these strategies, focusing on the most recent discoveries. The study of prokaryotic defenses not only sheds light on microbial evolution but also uncovers novel enzymatic activities with promising biotechnological applications.
Topics: Prokaryotic Cells; Plasmids; Bacteriophages; Genome; Interspersed Repetitive Sequences
PubMed: 37347666
DOI: 10.1016/j.celrep.2023.112672 -
Journal of Molecular Biology Apr 2023CRISPR-Cas are prokaryotic defence systems that provide protection against invasion by mobile genetic elements (MGE), including bacteriophages. MGE can overcome... (Review)
Review
CRISPR-Cas are prokaryotic defence systems that provide protection against invasion by mobile genetic elements (MGE), including bacteriophages. MGE can overcome CRISPR-Cas defences by encoding anti-CRISPR (Acr) proteins. These proteins are produced in the early stages of the infection and inhibit the CRISPR-Cas machinery to allow phage replication. While research on Acr has mainly focused on their discovery, structure and mode of action, and their applications in biotechnology, the impact of Acr on the ecology of MGE as well as on the coevolution with their bacterial hosts only begins to be unravelled. In this review, we summarise our current understanding on the distribution of anti-CRISPR genes in MGE, the ecology of phages encoding Acr, and their coevolution with bacterial defence mechanisms. We highlight the need to use more diverse and complex experimental models to better understand the impact of anti-CRISPR in MGE-host interactions.
Topics: Bacteria; Bacteriophages; CRISPR-Cas Systems; Evolution, Molecular; Models, Theoretical; Viral Proteins; Interspersed Repetitive Sequences
PubMed: 36690071
DOI: 10.1016/j.jmb.2023.167974 -
Cellular and Molecular Life Sciences :... Sep 2010Bacteria such as Staphylococcus aureus are successful as commensal organisms or pathogens in part because they adapt rapidly to selective pressures imparted by the human... (Review)
Review
Bacteria such as Staphylococcus aureus are successful as commensal organisms or pathogens in part because they adapt rapidly to selective pressures imparted by the human host. Mobile genetic elements (MGEs) play a central role in this adaptation process and are a means to transfer genetic information (DNA) among and within bacterial species. Importantly, MGEs encode putative virulence factors and molecules that confer resistance to antibiotics, including the gene that confers resistance to beta-lactam antibiotics in methicillin-resistant S. aureus (MRSA). Inasmuch as MRSA infections are a significant problem worldwide and continue to emerge in epidemic waves, there has been significant effort to improve diagnostic assays and to develop new antimicrobial agents for treatment of disease. Our understanding of S. aureus MGEs and the molecules they encode has played an important role toward these ends and has provided detailed insight into the evolution of antimicrobial resistance mechanisms and virulence.
Topics: Drug Resistance, Bacterial; Genomic Islands; Humans; Interspersed Repetitive Sequences; Staphylococcus aureus
PubMed: 20668911
DOI: 10.1007/s00018-010-0389-4 -
Intervirology 2010Giant viruses or nucleocytoplasmic large DNA viruses (NCLDVs) infect a wide range of eukaryotic hosts (including, algae, amoebae and metazoans) and show a very large... (Review)
Review
Giant viruses or nucleocytoplasmic large DNA viruses (NCLDVs) infect a wide range of eukaryotic hosts (including, algae, amoebae and metazoans) and show a very large range in genome size (between 100 kb and 1.2 Mb). Here we review some recent results concerning the extensive lateral gene transfer which appears to have occurred during NCLDV evolution. Current data suggest that giant viruses probably originated from a simple and ancient viral ancestor with a small subset of 30-35 genes encoding replication and structural proteins. A large array of lateral gene transfers from diverse cellular sources, including several families of mobile genetic elements, is probably responsible for the huge diversity of genome size and composition found in extant giant viruses.
Topics: Amoeba; DNA, Viral; Eukaryota; Evolution, Molecular; Gene Transfer, Horizontal; Interspersed Repetitive Sequences; Recombination, Genetic; Viruses
PubMed: 20551687
DOI: 10.1159/000312920 -
Microbial Biotechnology Jan 2024Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids,... (Review)
Review
Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids, integrative and conjugative elements, transposons, insertion sequences and bacteriophages. Notably, the spread of antimicrobial resistance genes (ARGs), which poses a serious threat to public health, is primarily attributable to HGT through MGEs. This mini-review aims to provide an overview of the mechanisms by which MGEs mediate HGT in microbes. Specifically, the behaviour of conjugative plasmids in different environments and conditions was discussed, and recent methodologies for tracing the dynamics of MGEs were summarised. A comprehensive understanding of the mechanisms underlying HGT and the role of MGEs in bacterial evolution and adaptation is important to develop strategies to combat the spread of ARGs.
Topics: Interspersed Repetitive Sequences; Gene Transfer, Horizontal; Plasmids; Bacteria; Bacteriophages; Anti-Bacterial Agents
PubMed: 38226780
DOI: 10.1111/1751-7915.14408