China
Africa
Explore chapters and articles related to this topic
Science of biotechnology – Recombinant DNA technology
Published in Ronald P. Evens, Biotechnology, 2020
The circular plasmid DNA must be cut open to accept the human DNA (gene) using unique bacterial enzymes (restriction endonucleases). Each endonuclease enzyme is highly specific to a certain nucleic acid sequence, creating a very specific cut, that is, an opening in the DNA plasmid structure appropriate for a specific gene’s incorporation and permitting efficient recombination. DNA materials will recombine naturally with the human gene sequence inserted into the circular plasmid sequence. A DNA ligase enzyme is employed to enhance the DNA recombination process. Figure 2.9 displays such restriction endonuclease enzymes found in nature in specific bacteria as noted. The very high specificity to an individual DNA sequence of nucleotides for endonucleases is shown in Figure 2.9.
Oncogenes and Cancer
Published in Pimentel Enrique, Oncogenes, 2020
It has been recognized that DNA recombination and gene rearrangements may play a central role in the normal processes of cellular differentiation,276 which is probably also valid in abnormal cell differentiation leading to neoplasia. The possible role of specific chromosome translocations in the origin of hematologic malignant diseases remains undetermined but the high frequency of their occurrence suggest that these translocations are important for the origin and/or development of the respective malignancies. However, these translocations are heterogeneous at the molecular level and they are not present in some cases of the particular diseases. No consistent patterns of altered expression of the translocated proto-oncogenes, c-abl in chronic myelogenous leukemia, and c-myc in B-cell lymphomas, have been found. Rather, in at least some of these tumors the coding sequences of the translocated proto-oncogenes may be unaltered and their polypeptide products may be qualitatively normal and may be produced in normal amount in the tumor cells.
Mechanisms of Resistance to Antineoplastic Drugs
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Philip J. Vickers, Alan J. Townsend, Kenneth H. Cowan
Schimke114-116 has proposed that both HSRs and DMs arise by the same events. First, overreplication of DNA occurs by multiple initiations of DNA replication. The initial reduplication of DNA is apparently followed by a step involving DNA recombination. When the recombination event occurs chromosomally, an HSR may develop at the site of the integrated gene. When this event occurs extrachromosomally, a DM is formed. It has been suggested that homologous recombination of the amplified DNA sequences that are transiently formed may result in a number of other cytogenetic aberrations in addition to HSRs and DMs, including sister chromatid exchanges, dicentric chromosomes, and chromosomal inversions.116
Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents
Published in Expert Opinion on Therapeutic Patents, 2023
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D’Agostino
Rhodesian (TbrCATL) belongs to the family of cathepsin L (CATL)-like proteases usually found in the parasite lysosomes and is important for survival, infectivity, and CNS penetration. It possesses a conserved catalytic triad (Cys/His/Asn) within its single chain of 215 peptidic residues [83], able to degrade both protozoan and host proteins, among which the variant surface glycoproteins (VSGs) of the parasite coat and protective immunoglobulins to escape the host immune system [84–86]. Antigenic variation in these VSGs is the main pathogenetic mechanism in T. brucei mediated by regular switching to maintain prolonged infections by bloodstream trypomastigotes [87]. Moreover, proteins involved in DNA recombination include RAD51, which mediates strand invasion in homologous recombination, RAD51-3, and BRCA2 that facilitate VSG switching, and proteins involved in DNA metabolism suppressing VSG switching. TRF and RAP1 are two telomere proteins with unique nucleic acid-binding activities, vital for T. brucei. In addition, TRF and RAP1 play crucial roles in antigenic variation; indeed, several telomere proteins have been identified in T. brucei. TbTRF is the duplex TTAGGG repeat binding factor and a TRF homolog; it associates with the telomere throughout the cell cycle, thus indicating the importance of TRF for the terminal telomere structure and cell proliferation [88]; defects in telomere integrity maintenance allow more VSG switching. TbRAP1 is a homolog of yeast and mammalian RAP1s.
Investigation of genotoxic effects of paraben in cultured human lymphocytes
Published in Drug and Chemical Toxicology, 2019
Devrim Güzel Bayülken, Berrin Ayaz Tüylü, Handan Sinan, Hülya Sivas
Unlike other test results, paraben did not lead to significant increase the mean number of SCE per cell in both treatment time. SCE test is useful for assessing the cytogenic impacts of clastogenic agents on chromosomes. They are formed through DNA post-replication repair following DNA damage and may arise during mitosis by agents that interfere with DNA recombination (Norppa et al.2006). The frequency of SCEs has been used to identify genotoxic agents (Perry and Thompson 1984). Tayama et al. (2008) conducted on propyl and butyl p-hydroxybenzoate to determine their genotoxicity on CHO-K1 cells using sister-chromatid exchange (SCE), chromosome aberration (CA), and DNA strand break (comet) assays. Chromosome aberrations and sister chromatid exchange have been reported in CHO-K1 cells exposed to propyl paraben at concentrations of 500 µM and above. Also, these chemicals caused DNA migration in the comet assay. Induction of CA and Comet have similarity with our findings.
Isolation and characterization of a monoclonal antibody containing an extra heavy-light chain Fab arm
Published in mAbs, 2018
Dan Boyd, Arpa Ebrahimi, Sarah Ronan, Brian Mickus, Matthew Schenauer, Jenny Wang, Darren Brown, Alexandre Ambrogelly
Here, we purified, characterized and identified a new mAb-related structure observed in SEC profiles from a preparation of an early-stage recombinant mAb produced by a CHO cell line. The variant consisted of a canonical mAb monomer associated in a non-covalent fashion with a Fab arm amputated from its Fc domain. The truncated heavy chain is encoded in the cell line genome. This variant is the product of a DNA recombination event that occurred during the insertion of the transgene construct and amplification steps and was propagated during cell line selection. While this particular modification has not been described to date, it adds to the long list of variants described in the literature for the many mAbs that are approved or under clinical development.1-3