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Antibiotics: The Need for Innovation
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Protein synthesis is orchestrated by the cell’s DNA. An enzyme called DNA helicase separates the strands at a specific region on the DNA molecule; the gene containing the instruction for a specific protein, such as those like β-lactamase, which give rise to resistance. DNA helicase breaks the hydrogen bonds between the DNA bases, enabling another enzyme, called RNA polymerase to move along the template DNA strand and bind the exposed bases to complementary nucleotides that are present in the cell. This process is known as transcription and results in the production of a stand of RNA, which carries a complementary sequence of bases to the template gene on the DNA.
Bloom Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Structurally, BLM consists of the N-terminus (consisting of several short acid patches and also a region required for strand exchange), the topoisomerase IIIα-binding region, the ssDNA strand-annealing and strand exchange domain, the DNA helicase domain, the RecQ C-terminal domain (including the Zn2+-binding motif, winged helix), the helicase and ribonuclease D C-terminal domain, and the nuclear localization signal. Functionally, the N-terminus binds to interaction partners such as TOP3α, RMI1/2, and RAD51; the DNA helicase domain is responsible for ATP binding and hydrolysis; the RecQ C-terminal domain acts as a dsDNA-binding site; the -hairpin located in the winged helix domain is responsible for the duplex separation; the helicase and ribonuclease D C-terminal domain interacts with the helicase domain to facilitate efficient ATP hydrolysis and DNA unwinding [9].
Role of Ascorbate and Dehydroascorbic Acid in Metabolic Integration of the Cell
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Gábor Bánhegyi, András Szarka, József Mandl
The shortage of ascorbate generated by ER luminal processes seems to also be present in the background of a human disease. Werner syndrome is a premature aging disorder caused by mutations in a RecQ-like DNA helicase (Wrn). Ascorbate supplementation proved to be beneficial in different models of the disease: in WS fibroblast [41], in Wrn mutant mice [4], and in wrn-1 Caenorhabditis elegans [24]. Mutant mice lacking part of the helicase domain of the Wrn ortholog exhibit several phenotypic features of Werner syndrome. Moreover, mislocalization of the Wrn mutant protein to the ER fraction was observed with increased oxidative stress and activation of the ER stress response [4]. When ascorbate synthesis of the mutant mice was abolished by knocking out the gulonolactone oxidase gene, double-mutant mice exhibited small size, sterility, osteopenia, and a severe reduction in life span. High doses of ascorbate improved the phenotype [5]. The results suggest that the ER-mislocalized Wrn protein increases the consumption or inhibits the uptake of ascorbate and DHA, activating the organellar stress. Further studies are needed to explore these possibilities.
Simple and feasible detection of hepatitis a virus using reverse transcription multienzyme isothermal rapid amplification and lateral flow dipsticks without standard PCR laboratory
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Mao-ling Sun, Yang Zhong, Xiao-na Li, Jun Yao, Yu-qing Pan
Several isothermal technologies have been developed for rapid, feasible nucleic detection. Multienzyme isothermal recombinase amplification (MIRA) is a novel nucleic acid amplification method based on recombinase polymerase amplification (RPA) [17]. This technique utilises four core proteins: recombinase-Rec A, DNA helicase-GP41, single-stranded binding (SSB) protein, and DNA pol I [18]. During amplification, helicase-GP41 and SSB form the D-Loop and start the reaction. Recombinase and DNA pol I then allow DNA extension rapidly at isothermal conditions. For RNA template amplification, specific primers can be used to directly synthesise cDNA using reverse transcriptase [19,20]. Simultaneously, the newly generated cDNA is used as a template for MIRA [21]. The whole reaction can be performed at 25 to 42 °C within 5 to 30 min without requiring complex instruments, providing a major advantage over conventional PCR. The lateral flow dipstick (LFD) can produce visually observable results in a relatively short time by hybridising with labelled colloidal gold [22]. Moreover, it provides a convenient, sensitive, and economical assay when combined with RT-MIRA.
Discovery of a novel Aurora B inhibitor GSK650394 with potent anticancer and anti-aspergillus fumigatus dual efficacies in vitro
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yuhua He, Wei Fu, Liyang Du, Huiqiao Yao, Zhengkang Hua, Jinyu Li, Zhonghui Lin
It is well known that ATP is the primary carrier of energy in cells. Upon hydrolysis, it releases energy from the chemical bonds to fuel cellular processes. For example, ATP hydrolysis by motor proteins or DNA helicases can induce conformational changes and thus drive the translocation of these proteins. In addition, the protein kinases regulate various biological processes by transferring a phosphate group from ATP to amino acid residues like serine, threonine, or tyrosine. Interestingly, the mitotic kinases Aurora B, Haspin, and Bub132 also possess intrinsic ATPase activity, producing free inorganic phosphate. It is currently unknown whether this energy-consuming activity has a physiological role in cells, further studies are needed to address this potentially interesting question.
Overexpression of long non-coding RNA MCM3AP-AS1 in breast cancer tissues compared to adjacent non-tumour tissues
Published in British Journal of Biomedical Science, 2021
A Riahi, M Hosseinpour-Feizi, A Rajabi, M Akbarzadeh, V Montazeri, R Safaralizadeh
One of the essential elements of pre-replication complexes is minichromosome maintenance (MCM) proteins that are composed of six-component complexes (MCM2-MCM7) by DNA helicase activities. These complexes are involved in the initiation and extension processes of DNA replication and lead to restrictions of DNA replication to once per cell cycle. Minichromosome maintenance complex component 3-associated protein (MCM3AP) is located at 21q22.3, and codes for a protein that binds to and acetylates MCM3 through acetyltransferase functions. The interaction of MCM3AP with MCM3 is crucial for not only its entry into the nucleus but also its binding to chromatin. Increased MCM3AP expression level plays a role in inhibiting the S phase of the cell cycle, and its regulatory role as a tumour suppressor gene with a low level of expression has been proved in breast cancer. MCM3AP-AS1 is a long non-coding RNA antisense1 for MCM3AP [16–19]. The roles and regulatory mechanisms of lncRNA MCM3AP-AS1 in breast cancer are unclear.