China
Africa
Explore chapters and articles related to this topic
Family Caulimoviridae
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
In contrast to the Baltimore class VI single-stranded RNA members of the order Ortervirales, which frequently integrate into the host genomes, the Baltimore class VII members of the family Caulimoviridae, as well of hepadnaviruses of the order Blubervirales described in Chapters 37 and 38, often referred together to as pararetroviruses (Hull and Will 1989), do not actively integrate into host chromosomes, while their episomal replication cycles do not involve an integration phase. However, the capture of pararetroviral DNA in host genomes, presumably by illegitimate recombination, is commonplace, particularly in plants, giving rise to the corresponding endogenous elements (Feschotte and Gilbert 2012; Diop et al. 2018; Krupovic et al. 2018).
Resistance Mechanisms of Tumor Cells
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Almost all hematological tumors do not exhibit such a mutational landscape rather than display recurrent chromosomal translocations that result in “chimeric fusion genes” (see Fig. 17.1, upper right panel B). These fusions genes are highly specific and prototypic for leukemia disease subtypes (ALL, AML, CML, and CLL). The term “chromosomal translocation” describes an illegitimate exchange of chromosome material between two or more non-homologous chromosomes. In most cases, these illegitimate events are caused by a DNA damage situation where a subsequent DNA repair process results in wrongly fused “derivative chromosomes” (Reichel et al., 1998; Richardson et al., 1998). Chromosomal translocations can be subcategorized by the results of their illegitimate recombination event: (1) overexpression of proto-oncogenes by fusing them to strong enhancers, or (2) creation of chimeric fusion genes. Since these chromosomal changes occur recurrently at nearly precise points of our genomes, one might argue that these genes represent recombination hot spots. DNA damage situation may occur more frequently due to endogenous events (like, e.g., early apoptosis, torsional stress, DNase I hypersensitive sites, etc.) or exogenous xenobiotic stress conditions (Strick et al., 2000).
Mutagenic Consequences Of Chemical Reaction with DNA
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
The simplest mechanism would be loss of a section of chromosome by an illegitimate recombination event with itself. Such a mechanism, the Campbell model,158 can be invoked to explain the formation of F primes (F factors containing chromosomal bacterial genes) and specialized transducing particles (bacteriophage particles which include bacterial genes). It can, however, hardly be general, since deletion mutagenesis occurs apparently normally in recombination deficient bacteria.159
Bacterial death from treatment with fluoroquinolones and other lethal stressors
Published in Expert Review of Anti-infective Therapy, 2021
The subunit dissociation idea, which was originally used to explain gyrase-mediated illegitimate recombination [32], is supported by several observations. In one, a two-amino-acid deletion near a GyrB-GyrB interface reduces the inhibitory effect of chloramphenicol on oxolinic acid-mediated killing [40], presumably increasing the contribution of the subunit-dissociation mode. In a similar experiment, a GyrA A67S substitution renders nalidixic acid lethal in the presence of chloramphenicol [33] (this property is not seen with wild-type cells). GyrA-67 is located near the GyrA-GyrA interface, and substitution of Ser for Ala is expected to weaken the contact. A third line of support derives from isolated nucleoids. When gyrase is added to isolated nucleoids along with a potent fluoroquinolone, such as gatifloxacin, chromosome fragmentation is indicated by a drop in solution viscosity [33]. Nalidixic acid fails to lower viscosity unless the added gyrase carries the GyrA A67S substitution. Thus, an indirect case can be developed for subunit dissociation leading to chromosome fragmentation.
Track to the future: historical perspective on the importance of radiation track structure and DNA as a radiobiological target
Published in International Journal of Radiation Biology, 2018
In addition to the difference in energy deposition on the sub-micron scale, there are also significant differences on the micrometer/cellular scale between different radiation qualities which can play an important role in determining the biological response. For example, assuming an 8 μm diameter spherical cell, 1 Gy of low-LET radiation (e.g. γ-rays) corresponds to approximately 1000 electron tracks depositing energy essential randomly distributed across the volume. In contrast, 1 Gy of high-LET α-particle corresponds to ∼2–4 tracks traversing the cell, with highly heterogeneous energy deposition along these straight, narrow densely ionizing tracks (due to short range of the delta-electrons, the majority of energy is deposited ≪0.1 μm from the track). Therefore, the resulting 20–40 DSB produced by low-LET radiation will be essential homogeneously distributed across the nucleus and associated chromosomes. While for α-particles, the relatively similar number of DSB produced will be highly correlated along the narrow tracks as it traverses the nucleus, not only within individual chromosomes but also between adjacent chromosome territories traversed (Figure 1). As a result of the correlation of these breaks in time and space increasing the probability of genetic rearrangements between these sites, complex chromosome aberrations (requiring three or more breaks in two or more chromosomes; see Figure 5) are characteristically produced by high-LET particles (Anderson et al. 2002). In contrast to the production of mainly simple chromosome aberrations (maximum of two breaks in two chromosomes, see Figure 5) observed for low doses of X-rays, a wide spectrum of aberrations result from a single α-particle traversal (for peripheral blood lymphocytes an average complex will typical involve six breaks in four chromosomes). However, the variation in nuclear geometry with respect to this track will also influence the resulting yields and complexity of aberrations (Durante et al. 2010). The likelihood of aberrations being classified as complex, as opposed to simple, was found to increase with decreasing α-particle energy, as a result of increasing ionization density (LET) and the associated increase in frequency and complexity of DSB along the track (Anderson et al. 2007). The importance of the spatial distribution of dose deposition and therefore DNA breaks across the nucleus on the micrometer scale in determining biological response has recently been demonstrated recently using patterned delivery of 20 MeV protons (Schmid et al. 2012). It was observed that the RBE for micronuclei and dicentrics were significantly raised when the protons were focused to submicron spots delivered in a 5.4 × 5.4 μm2 matrix compared to the same dose delivered using a quasi-homogeneous 1 × 1 μm2 matrix distribution. The probability of illegitimate recombination between breaks increasing when they are concentrated in the sub-micrometer spots.