MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis.

Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS-STING-mediated signalling and tumour suppression. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA). Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation.

Mechanisms of Immune Sensing of DNA Damage.

Genomic stability relies on a multifaceted and evolutionarily conserved DNA damage response (DDR). In multicellular organisms, an integral facet of the DDR involves the activation of the immune system to eliminate cells with persistent DNA damage. Recent research has shed light on a complex array of nucleic acid sensors crucial for innate immune activation in response to oncogenic stress-associated DNA damage, a process vital for suppressing tumor formation.

TPX2 Amplification-Driven Aberrant Mitosis in Culture Adapted Human Embryonic Stem Cells with gain of 20q11.21.

Background: Despite highly effective machinery for the maintenance of genome integrity in human embryonic stem cells (hESCs), the frequency of genetic aberrations during in-vitro culture has been a serious issue for future clinical applications.

Method: By passaging hESCs over a broad range of timepoints (up to 6 years), the isogenic hESC lines with different passage numbers with distinct cellular characteristics, were established.

Result: We found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs) with normal copy number.

Dual inhibition of DNA-PK and DNA polymerase theta overcomes radiation resistance induced by p53 deficiency.

 deficiency in cancer is associated with poor patient outcomes and resistance to DNA damaging therapies. However, the mechanisms underlying treatment resistance in p53-deficient cells remain poorly characterized. Using live cell imaging of DNA double-strand breaks (DSBs) and cell cycle state transitions, we show that p53-deficient cells exhibit accelerated repair of radiomimetic-induced DSBs arising in S phase.

The cGAS/STING/TBK1/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels.

Chromosomal instability (CIN) in cancer cells has been reported to activate the cGAS-STING innate immunity pathway via micronuclei formation, thus affecting tumor immunity and tumor progression. However, adverse effects of the cGAS/STING pathway as they relate to CIN have not yet been investigated. We addressed this issue using knockdown and add-back approaches to analyze each component of the cGAS/STING/TBK1/IRF3 pathway, and we monitored the extent of CIN by measuring micronuclei formation after release from nocodazole-induced mitotic arrest.

The Effects of Addition Timing of NaCl and Sodium Tripolyphosphate and Cooking Rate on Pink Color in Cooked Ground Chicken Breasts.

The current study investigated the effects of timing of NaCl (2%) and sodium tripolyphosphate (STPP, 0.5%) addition and cooking rates on color and pigment properties of ground chicken breasts. Four treatments were tested as follows: treatment 1, no NaCl and STPP added and stored for 7 d; treatment 2, NaCl+STPP added on 0 d and stored for 7 d; treatment 3, NaCl added on 0 d and STPP added on 7 d; and treatment 4, stored for 7 d and NaCl+STPP added.

Presalting Condition Effects on the Development of Pink Color in Cooked Ground Chicken Breasts.

The effects of presalting conditions (storage temperature and duration) with/without sodium tripolyphosphate (STPP) on the color and pigment characteristics of cooked ground chicken breast were investigated. Meat mixtures containing 2% NaCl (control) or 2% NaCl and 0.5% STPP (STPP treatment) were stored for 0, 3, 5, 7, and 10 d at 2°C or 7°C, followed by cooking to 75°C, and cooling and storage at 2°C-3°C until further analysis.

Inhibition of PP2A activity by HO during mitosis disrupts nuclear envelope reassembly and alters nuclear shape.

Many types of cancer cells exhibit abnormal nuclear shapes induced by various molecular changes. However, whether reactive oxygen species (ROS) induce nuclear deformation has not been fully addressed. Here, we show that hydrogen peroxide (HO) treatment induced concentration-dependent alterations in nuclear shape that were abolished by pretreatment with the antioxidant N-acetyl-L-cysteine or by catalase overexpression.

MED28 Over-Expression Shortens the Cell Cycle and Induces Genomic Instability.

The mammalian mediator complex subunit 28 (MED28) is overexpressed in a variety of cancers and it regulates cell migration/invasion and epithelial-mesenchymal transition. However, transcription factors that increase MED28 expression have not yet been identified. In this study, we performed a luciferase reporter assay to identify and characterize the prospective transcription factors, namely E2F transcription factor 1, nuclear respiratory factor 1, E-26 transforming sequence 1, and CCAAT/enhancer-binding protein β, which increased MED28 expression.

Effects of Calcium Powder Mixtures and Binding Ingredients as Substitutes for Synthetic Phosphate on the Quality Properties of Ground Pork Products.

This study aimed to investigate the combined effect of using natural calcium mixtures and various binding ingredients as replacers for synthetic phosphate in ground pork products. We performed seven treatments: control (0.3% phosphate blend), treatment 1 (0.

Effect of NaCl Concentration and Cooking Temperature on the Color and Pigment Characteristics of Presalted Ground Chicken Breasts.

This study was conducted to determine the effects of NaCl concentration and cooking temperature on the color and pigment characteristics of presalted ground chicken breasts. Four treatments with different salt concentrations (0%, 1%, 2%, and 3%) were prepared and stored for 7 d prior to cooking. Each sample was cooked to four endpoint temperatures (70°C, 75°C, 80°C, and 85°C).

ATP depletion during mitotic arrest induces mitotic slippage and APC/C-dependent cyclin B1 degradation.

ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN did not arrest mitotic progression.

Egg Shell and Oyster Shell Powder as Alternatives for Synthetic Phosphate: Effects on the Quality of Cooked Ground Pork Products.

This study aimed to determine the optimal ratio of natural calcium powders (oyster shell and egg shell calcium) as synthetic phosphate replacers in pork products. Ground pork samples were subjected to six treatments, as follows: control (-) (no phosphate added), control (+) (0.3% phosphate blend added), treatment 1 (0.

Effects of Various Calcium Powders as Replacers for Synthetic Phosphate on the Quality Properties of Ground Pork Meat Products.

The aim of this study was to identify the optimal and superior type of natural calcium for replacing phosphate in cooked ground pork products. To achieve this, 0.5% eggshell calcium (ESC), oyster shell calcium (OSC), marine algae calcium (MAC), or milk calcium (MC) was added to ground pork meat products.

DNA double-strand breaks and Aurora B mislocalization induced by exposure of early mitotic cells to HO appear to increase chromatin bridges and resultant cytokinesis failure.

Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated.

A putative pH-dependent nuclear localization signal in the juxtamembrane region of c-Met.

The C-terminal fragment of the c-Met receptor tyrosine kinase is present in the nuclei of some cells irrespective of ligand stimulation, but the responsible nuclear localization signal (NLS) has not been previously reported. Here, we report that two histidine residues separated by a 10-amino-acid spacer (H1068-H1079) located in the juxtamembrane region of c-Met function as a putative novel NLS. Deletion of these sequences significantly abolished the nuclear translocation of c-Met, as did substitution of the histidines with alanines.