Aberrant recombination

Hochtl, J. Zachau, H.G. (1983). A novel type of aberrant recombination in immunoglobulin genes and its implications for V-J joining mechanism. Nature 302,260-263. 

Further studies have implicated BRCAl in the cellular response to DNA double-stranded breaks (DSBs), a potentially lethal form of DNA damage. Cells defective in BRCAl possess numerous cytological and biological features that have been known for years to be correlated with perturbation in the maintenance of chromosome stability. This includes aneuploidy, centrosome amplification, spontaneous chromosome breakage, aberrant recombination events, sensitivity to ionizing radiation, and impaired cell cycle checkpoints. In addition, a variety of experiments have demonstrated roles for BRCAl in enforcing the GfM cell cycle transition, homologous recombination between sister chromatids, as well as the restart of stalled replication in S phase. 

Quite recently emerged the antitumor strategy based on the use of small molecules that specifically target telomeres and telomerase [1 ]. Telomeres are gua-nine-rich DNA sequences localized at the ends of the chromosomes. They protect chromosomal DNA from degradation, prevent end-to-end fusion and other forms of aberrant recombination, and allow it to be completely replicated without loss of genetic material. The length of the telomeres correlates with the ability of a cell to... 

Mammalian cells Cultured human lymphocytes Mitotic recombination Aberrant metaphases No data - L Vova 1984... 

As compared to DCs, B cells are very poor APCs and play a major role as source for antibodies. Upon stimulation by antigens and in the presence of T cells at the border of the T-cell-B-cell area, adjacent to follicles, B cells become antibody-secreting cells and eventually form a germinal center (GC) response. GCs are specialized follicles for B-cell expansion, somatic hypermutation, and class switch recombination, processes that are regulated by T cells, follicular DCs, and other cells. In this process of B-cell maturation, Tregs seem to play a critical role, as in several immune diseases, which are characterized by aberrant antibody... 

Fortunately, a number of in situ, short-term bioassays to detect genotoxic and related effects have become available. These include a variety of measured endpoints such as aneuploids, chromosal aberrations, DNA damage, dominant lethal mutation, gene mutation, inhibition of intercellular communication, micronuclei, mitotic recombination and gene conversions, and sister chromatid exchange and cell transformation (IARC, 1989). A detailed discussion of these tests is beyond the scope of this book. However, such tests are important from our perspective as atmospheric chemists because, as we shall see, they can be used to detect biologically active compounds in very complex mixtures, and hence serve to focus chemical analysis efforts (IARC, 1989, p. 20). We emphasize in advance the... 

Epoxybutane induced morphological transformation, sister chromatid exchanges, chromosomal aberrations and mutation in cultured animal cells however, in a single study, it did not induce unscheduled DNA synthesis in rat primary hepatocytes. It induced sex-linked recessive lethal mutations and translocations in Drosophila melanogaster, mitotic recombination in yeast, and mutations in yeast and fungi. 1,2-Epoxybutane induced DNA damage and mutations in bacteria. 

Propanc sultone causes DNA damage and mutation in bacteria and induces mitotic recombination in yeast. It induces mutations and chromosomal aberrations in plant cells. In cultured mammalian cells, it induces chromosomal aberrations, sister chromatid exchanges and, according to single studies, cell transfonnation in C3H lOT /z cells, but not in Syrian hamster embryo cells. DNA strand breaks are induced in brain cells from rats injected with 1,3-propane sultone. 

As previously summarized, diethyl sulfate induced mutation and DNA damage in bacteria and induced reverse mutation and mitotic recombination in yeast. In plant cells, diethyl sulfate induced chromosomal aberrations. In a single study, diethyl sulfate did not induce heritable translocation in Drosophila melanogaster but did induce autosomal recessive lethal mutations, sex-linked recessive lethal mutations and genetic crossing-over. In cultured mammalian cells, diethyl sulfate induced chromosomal aberrations, mieronueleus formation, sister chromatid exchanges, forward mutation and DNA singlestrand breaks it also induced unscheduled DNA synthesis in primary cultures of rat... 

Mismatch repair was an essential component of the Holliday model for meiotic recombination in fungi (Holliday, 1965a). This states that recombination depends on the formation of relatively short stretches of hybrid DNA between homologous chromatids within which, if they spanned a region of heterozygosity, a mispaired base-pair would appear. Mismatch repair would determine whether or not aberrant segregations would be found in the tetrads formed on completion of meiosis. 

Although the physiological function of IL-20 has not been identified, three lines of evidence support a role for IL-20 and its receptor in inflammatory skin diseases such as psoriasis. For example, overexpression of IL-20 in transgenic mice results in neonatal lethality with skin abnormalities similar to those observed in human psoriatic skin (Bll). These include several hallmark characteristics of this multigenic diseases such as increased proliferation of keratinocytes in the basal and the suprabasal layers of the epidermis, aberrant epidermal differentiation, and infiltration of immune cells into the skin (R3). Recombinant IL-20 protein... 

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