The protein kinase ataxia-telangiectasia mutated (ATM) is best known for its role as an apical activator of the DNA damage response in the face of DNA double-strand breaks (DSBs). Following induction of DSBs, ATM mobilizes one of the most extensive signalling networks that responds to specific stimuli and modifies directly or indirectly a broad range of targets. Although most ATM research has focused on this function, evidence suggests that ATM-mediated phosphorylation has a role in the response to other types of genotoxic stress. Moreover, it has become apparent that ATM is active in other cell signalling pathways involved in maintaining cellular homeostasis.

The ATM protein kinase: regulating the cellular response to genotoxic stress, and more

DNA double-stranded breaks (DSB) are among the most dangerous forms of DNA damage. Unrepaired DSBs results in cells undergoing apoptosis or senescence whereas mis-processing of DSBs can lead to genomic instability and carcinogenesis. One important pathway in eukaryotic cells responsible for the repair of DSBs is non-homologous end-joining (NHEJ). In this review we will discuss the interesting new insights into the mechanism of the NHEJ pathway and the proteins which mediate this repair process. Furthermore, the general role of NHEJ in promoting genomic stability will be discussed.

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DNA double strand break repair via non-homologous end-joining

The DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and the Ku70/80 heterodimer. Over the past two decades, significant progress has been made in elucidating the role of DNA-PK in non-homologous end joining (NHEJ), the major pathway for repair of ionizing radiation-induced DNA double strand breaks in human cells and recently, additional roles for DNA-PK have been reported. In this review, we will describe the biochemistry, structure and function of DNA-PK, its roles in DNA double strand break repair and its newly described roles in mitosis and other cellular processes.

The DNA-dependent protein kinase: A multifunctional protein kinase with roles in DNA double strand break repair and mitosis

A DNA double-strand break (DSB) has long been recognized as a severe cellular lesion, potentially representing an initiating event for carcinogenesis or cell death. The evolution of DSB repair pathways as well as additional processes, such as cell cycle checkpoint arrest, to minimize the cellular impact of DSB formation was, therefore, not surprising. However, the depth and complexity of the DNA damage responses being revealed by current studies were unexpected. Perhaps the most surprising finding to emerge is the dramatic changes to chromatin architecture that arise in the DSB vicinity. In this review, we overview the cellular response to DSBs focusing on DNA repair pathways and the interface between them. We consider additional events which impact upon these DSB repair pathways, including regulated arrest of cell cycle progression and chromatin architecture alterations. Finally, we discuss the impact of defects in these processes to human disease.

The Repair and Signaling Responses to DNA Double-Strand Breaks

The clinical impact of deficiency in DNA non-homologous end-joining.

Human polynucleotide kinase/phosphatase (PNKP) is a dual specificity 5′-DNA kinase/3′-DNA phosphatase, with roles in base excision repair, DNA single-strand break repair and non-homologous end joining (NHEJ); yet precisely how PNKP functions in the repair of DNA double strand breaks (DSBs) remains unclear. We demonstrate that PNKP is phosphorylated by the DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Ionizing radiation (IR)-induced phosphorylation of cellular PNKP on S114 was ATM dependent, whereas phosphorylation of PNKP on S126 required both ATM and DNA-PK. Inactivation of DNA-PK and/or ATM led to reduced PNKP at DNA damage sites in vivo. Cells expressing PNKP with alanine or aspartic acid at serines 114 and 126 were modestly radiosensitive and IR enhanced the association of PNKP with XRCC4 and DNA ligase IV; however, this interaction was not affected by mutation of PNKP phosphorylation sites. Purified PNKP protein with mutation of serines 114 and 126 had decreased DNA kinase and DNA phosphatase activities and reduced affinity for DNA in vitro. Together, our results reveal that IR-induced phosphorylation of PNKP by ATM and DNA-PK regulates PNKP function at DSBs.

Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage

https://doi.org/10.1016/j.ultsonch.2022.106259

The preservable effects of ultrasound-assisted alginate oligosaccharide soaking on cooked crayfish subjected to Freeze-Thaw cycles

Abstract To explore the damage mechanisms of freeze-thaw cycles on cooked crayfish in frozen storage, changes in the physicochemical properties and structure of cooked crayfish during the freeze-thaw cycles were investigated. The physicochemical properties of cooked crayfish changed significantly after five freeze-thaw cycles. The moisture content, water holding capacity, pH, and textural properties were decreased, while the total color difference, drip loss, and protein and lipid oxidation were significantly increased ( P &lt; 0.05). LF-NMR and MRI verified the water loss, and SDS-PAGE showed denaturation/degradation of myofibrillar proteins (MPs). Multiple freeze-thaw cycles promoted the transition from α-helix to β-turn in the secondary structure, the unfolding of tertiary structure, and a significant change in the chemical forces of MPs. SEM results revealed a disruption in the microstructure of muscle fibers. Repeated freeze-thaw cycles reduced the moisture content and distorted the structure of MPs in cooked crayfish, resulting in the disruption of physicochemical properties and its structure. Graphical Abstract 

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Effects of freeze-thaw cycles on physicochemical properties and structure of cooked crayfish (Procambarus clarkii)

The combined effects of ultrasound and plasma-activated water on microbial inactivation and quality attributes of crayfish during refrigerated storage.

The purpose of this study is to obtain a bio-based coating with good functional activity and self-healing ability, demonstrating its potential in food, materials, and other application fields. Plastic coatings can cause serious environmental pollution. It was a good solution to replace plastic coatings with degradable coatings. However, the development of degradable coatings in the fields of food and materials was limited due to their insufficient antibacterial ability and weak comprehensive properties. Therefore, chitosan nanoparticles (NPs) loaded with gallic acid (GA) were self-assembled with gelatin (GE) to prepare high-performance, degradable, self-healing bio-based nanocomposite coatings with antibacterial and antioxidant properties. The oxygen permeability of GE nanocomposite coatings decreased gradually with the addition of NPs, and the barrier properties increased significantly. At the same time, due to the excellent antioxidant and antibacterial ability of GA, the antioxidant effect of the nanocomposite coatings increased by 119%, and the antibacterial rate against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) increased by 32% and 58%, respectively, compared with the pure GE coatings. In addition, the nanocomposite coatings can be repaired within 24 h after being scratched at room temperature. Finally, GA coated with chitosan nanoparticles can significantly delay the escape of GA, and the retardation of gallic acid release exceeded 89% in simulated solutions after 24 h immersion, extending the service life of the nanocomposite coatings.

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Chen Wang

Papers

Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage

The preservable effects of ultrasound-assisted alginate oligosaccharide soaking on cooked crayfish subjected to Freeze-Thaw cycles

Effects of freeze-thaw cycles on physicochemical properties and structure of cooked crayfish (Procambarus clarkii)

The combined effects of ultrasound and plasma-activated water on microbial inactivation and quality attributes of crayfish during refrigerated storage.

High-Performance, Degradable, Self-Healing Bio-Based Nanocomposite Coatings with Antibacterial and Antioxidant Properties