DNA Genome Stability Research Articles

PTBP1 Regulates DNMT3B Alternative Splicing by Interacting With RALY to Enhance the Radioresistance of Prostate Cancer.

Radiotherapy is a curative arsenal for prostate cancer (PCa), but radioresistance seriously compromises its effectiveness. Dysregulated RNA splicing factors are extensively involved in tumor progression. Nonetheless, the role of splicing factors in radioresistance remains largely unexplored in PCa. Here, 23 splicing factors that are differentially expressed between PCa and adjacent normal tissues across multiple public PCa databases are identified. Among those genes, polypyrimidine tract binding protein 1 (PTBP1) is significantly upregulated in PCa and is positively associated with advanced clinicopathological features and poor prognosis. Gain- and loss-of-function experiments demonstrate that PTBP1 markedly reinforces genomic DNA stability to desensitize PCa cells to irradiation in vitro and in vivo. Mechanistically, PTBP1 interacts with the heterogeneous nuclear ribonucleoproteins (hnRNP) associated with lethal yellow protein homolog (RALY) and regulates exon 5 splicing of DNA methyltransferase 3b (DNMT3B) from DNMT3B-S to DNMT3B-L. Furthermore, upregulation of DNMT3B-L induces promoter methylation of dual-specificity phosphatase-2 (DUSP2) and subsequently inhibits DUSP2 expression, thereby increasing radioresistance in PCa. The findings highlight the role of splicing factors in inducing aberrant splicing events in response to radiotherapy and the potential role of PTBP1 and DNMT3B-L in reversing radioresistance in PCa.

Yttrium oxide nanoparticles ameliorates calcium hydroxide and calcium titanate nanoparticles induced genomic DNA and mitochondrial damage, ROS generation and inflammation

Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic effects.

Phytoremediation and genetic adaptation potential of Jatropha curcas on heavy metals enriched mine tailings

BackgroundPhytoremediation is aninexpensive green method that uses metal-tolerant plants to extract these contaminants and restore the soil. MethodsThe phytoremediation potential and genomic DNA/genetic adaptability nature of Jatropha curcas was investigated by 90 days of greenhouse experiment.The genomic DNA stability was determined through RAPD analysis. Soil characterization results the magnesite mine tailing physicochemical parameters (pH, Total carbon, Total hardness, NPK, Cr, Pb, Mn, and Cd) were beyond the acceptable limits. Thus, the mine soil diluted with fertile soil (group a-f) to create different treatment groups. Significant FindingsThe results stated that soil diluted with maximum quantity of fertile soil showed maximum growth and considerably extracted the metals from the soil compared to undiluted (group e) soil and other groups. The BAF and TF values strongly suggests that the J.curcas is suitable candidature with phytoextraction potential. The RAPD analysis on whole genomic DNA revealed that the plan possesses considerable metal adaptation potential under metal stress condition confirmed by GTS and DNA polymorphism analyses through RAPD and also TSP analyses. Hence, this J. curcas can be employed as considerable plant with phytoextraction (as hyperaccumulator) potential to remove the heavy metals from the soil.

Evaluation of accumulation and translocation of Pb and Cr in Vigna unguiculata by hydroponic phytoremediation model and assess it genetic stability

In this study, the phytoremediation (accumulation and translocation) competence of Pb and Cr by Vigna unguiculata under metal supplemented hydrophonic medium was investigated. Moreover, analyzed the genomic DNA stability of V. unguiculata under different dosages of Pb and Cr was analyzed through RAPD analysis. To assess the phytoextraction along with tolerance of V. unguiculata under Pb and Cr metal stress circumstances, a number of investigations were performed. The dosages of these metals reached maximum values (Pd: root 4685.8 ± 8.57 mg kg−1 & shoot 956.63 ± 3.9 mg kg−1, and Cr: root 5157.62 ± 11.56 mg kg−1 & 1243.51 ± 10.2 mg kg−1) in plant tissues in 1500 mg L−1 treatment. The Bioconcentration factors (BCF) for Pb as well as Cr demonstrated that V. unguiculata possess phytoextraction competence and the translocation factors (TCF) revealed that these metals were slightly translocated. This study indicates that, V. unguiculatais more appropriate for the phytoremediation of Pb and Cr polluted soil. However, the total soluble protein (TSP) and RAPD analysis revealed the occurrent of metal toxicity on TSP and plant genomic DNA. As a result of these findings, this V. unguiculata may be used for phytoremediation purposes; however, cultivation for edible purposes should be avoided in metal-contaminated soil because it adsorbs toxic metals that can spread to the food web while using this plant yield.

Nature can still be the strongest help against aging and neurodegeneration: the sirtuins way.

Nature can still be the strongest help against aging and neurodegeneration: the sirtuins way.

Noncanonical Mismatch Repair Protein NucS Modulates the Emergence of Antibiotic Resistance in Mycobacterium abscessus.

NucS/EndoMS-dependent noncanonical mismatch repair (MMR) ensures the stability of genomic DNA in mycobacteria and acts as a guardian of the genome by preventing the accumulation of point mutations. In order to address whether the inactivation of noncanonical MMR could increase the acquisition of drug resistance by mutation, a ΔnucS strain was constructed and explored in the emerging pathogen Mycobacterium abscessus. Deletion of nucS resulted in a mutator phenotype with increased acquisition of resistance to macrolides and aminoglycosides, the two main groups of antimycobacterial agents for M. abscessus treatment, and also to second-line drugs such as fluoroquinolones. Inactivation of the noncanonical MMR in M. abscessus led to increases of 10- to 22-fold in the appearance of spontaneous mutants resistant to the macrolide clarithromycin and the aminoglycosides amikacin, gentamicin, and apramycin, compared with the wild-type strain. Furthermore, emergence of fluoroquinolone (ciprofloxacin) resistance was detected in a nucS-deficient strain but not in a wild-type M. abscessus strain. Acquired drug resistance to macrolides and aminoglycosides was analyzed through sequencing of the 23S rRNA gene rrl and the 16S rRNA gene rrs from independent drug-resistant colonies of both strains. When the acquisition of clarithromycin resistance was examined, a different mutational profile was detected in the M. abscessus ΔnucS strain compared with the wild-type one. To summarize, M. abscessus requires the NucS-dependent noncanonical MMR pathway to prevent the emergence of drug-resistant isolates by mutation. To our knowledge, this is the first report that reveals the role of NucS in a human pathogen, and these findings have potential implications for the treatment of M. abscessus infections. IMPORTANCE Chronic infections caused by M. abscessus are an emerging challenge in public health, posing a substantial health and economic burden, especially in patients with cystic fibrosis. Treatment of M. abscessus infections with antibiotics is particularly challenging, as its complex drug resistance mechanisms, including constitutive resistance through DNA mutation, lead to high rates of treatment failure. To decipher the evolution of antibiotic resistance in M. abscessus, we studied NucS-dependent noncanonical MMR, a unique DNA repair pathway involved in genomic maintenance. Inactivation of NucS is linked to the increase of DNA mutations (hypermutation), which can confer drug resistance. Our analysis detected increased acquisition of mutations conferring resistance to first-line and second-line antibiotics. We believe that this study will improve the knowledge of how this pathogen could evolve into an untreatable infectious agent, and it uncovers a role for hypermutators in chronic infectious diseases under antibiotic pressure.

Eco-physiological response and genotoxicity induced by crude petroleum oil in the potential phytoremediator Vinca rosea L

BackgroundPhytoremediation is determined as an emerging green technology suitable for the safe remediation and restoration of polluted terrestrial and aquatic environments. In this study, the assessment of an ornamental plant, Vinca rosea L., as a phytoremediator of crude oil in polluted soils was conducted. In an open greenhouse experiment, plants were raised in sandy-clayey soils treated with 1, 3, 5, and 7% oil by weight. The experiment was conducted over 5 months. ResultsTotal petroleum hydrocarbon (TPH) degradation percentage by V. rosea after a 5-month growth period ranged from 86.83 ± 0.44% to 59.05% ± 0.45% in soil treated with 1 and 7%, respectively. Plants raised in polluted soils demonstrated a dramatic reduction in germination rates, in addition to growth inhibition outcomes shown from decreased plant height. An increase in branching was observed with an increase in oil pollution percentages. Moreover, the phytomass allocated to the leaves was higher, while the phytomass witnessed lower values for fine roots, flowering and fruiting when compared to the controls. Apart from the apparent morphological changes, there was a decrease in chlorophyll a/b ratio, which was inversely proportional to the oil pollution level. The contents of carotenoids, tannins, phenolics, flavonoids, and antioxidant capacity were elevated directly with an increase in oil pollution level. The start codon-targeted (SCoT) polymorphisms and inter-simple sequence repeat (ISSR) primers showed the molecular variations between the control and plants raised in polluted soils. The genetic similarity and genomic DNA stability were negatively affected by increased levels of crude oil pollution. ConclusionsThe ability of V. rosea to degrade TPH and balance the increased or decreased plant functional traits at the macro and micro levels of plant structure in response to crude oil pollution supports the use of the species for phytoremediation of crude oil-polluted sites. The genotoxic effects of crude oil on V. rosea still require further investigation. Further studies are required to demonstrate the mechanism of phenolic, flavonoid, and antioxidant compounds in the protection of plants against crude oil pollution stress. Testing different molecular markers and studying the differentially expressed genes will help understand the behavior of genetic polymorphism and stress-resistant genes in response to crude oil pollution.

Plant regeneration from root segments of Anthurium andraeanum and assessment of genetic fidelity of in vitro regenerates

A highly efficient regeneration system of Anthurium andraeanum Linden was established using root segments as explants of four genotypes, Arizona, SWD, OYH, and Mississippi. The root explants were firstly incubated on callus induction media containing NH4NO3 level of 206 mg L−1 or 825 mg L−1, and the calluses were formed from both ends of the root segments after 1 mo of culture. Root-derived calluses were then transferred to shoot regeneration media with NH4NO3 level of 412 mg L−1 or 1650 mg L−1, and numbers of shoot were successfully produced from the surface of calluses after 2 mo of culture. Medium containing 206 mg L−1 NH4NO3 induced more callus compared to 825 mg L−1. In contrast, the number of shoots per callus was the same between the above two shoot regeneration media indicating that NH4NO3 level had little effect on shoot regeneration. Long-termin vitro maintenance of the callus-bearing shoot initials was possible without compromising shoot regeneration and subsequent rooting. Histological analysis showed that early cell division was initiated from the inner cortical parenchyma cells near the vascular tissue and from the vascular parenchyma cells adjacent to the xylem vessel. The primary callus mainly comprised inner parenchyma cells with scattered procambial-like cells and xylem elements and two different meristematic zones beneath epidermal layers. Transfer of callus to the regenerative medium caused meristemoid formation and subsequent shoot primordia production. Calcium oxalate crystals and tannin-like deposits were visible on the outer callus layer or within the cotyledon-like structure of shoot primordium throughout callus development. Starch grains were abundant in root explants, but disappeared in the profusely growing primary callus, and were mobilized in the shoot primordium, indicating energy requirements of these two developmental stages. Flow cytometry analysis demonstrated that ploidy levels were maintained during in vitro cultures, including long-term regenerated plants. The inter-simple sequence repeat analysis indicated genomic DNA stability of Arizona and OYH but occasional genetic variation in primary regenerates of SWD and Mississippi.

Downregulation of DNA ligases in trophoblasts contributes to recurrent pregnancy loss through inducing DNA damages

IntroductionAs key components of DNA repair pathways, DNA ligases catalyze the formation of phosphodiester bonds between DNA single strands, which function as a “glue” to seal the DNA breaks. DNA ligases play important roles in almost all the normal physiological processes for maintaining the stability of genomic DNA, but their functions in recurrent pregnancy loss (RPL) are still unclear. MethodsImmunoblotting was used to determine protein level. DNA damages were examined by comet assay and cell viability was quantified by MTT assay. The cell apoptosis and cell cycle were examined by flow cytometry. The LIG4 mRNA degradation was quantified by qRT-PCR after actinomycin D treatment. The interactions between miRNAs and LIG4 were predicted by TargetScan and confirmed by dual luciferase assay. ResultsLIG1 and LIG4 were downregulated in RPL patients, while γH2AX level was upregulated. Knockdown LIG1 and LIG4 increased DNA damages in trophoblasts, which further induced apoptosis and cell cycle arrest. Serine/arginine-rich splicing factor 1(SRSF1) was reduced in RPL patients and positively correlated with LIG1. Knockdown SRSF1 increased the degradation of LIG1 mRNA which further repressed LIG1 expression. MiR-383 was upregulated in RPL patients and repressed LIG4 expression through interacting with 3′UTR of LIG4 mRNA. The level of miR-383 was found negatively correlated with LIG4 protein level in trophoblasts from RPL patients. DiscussionLIG1 and LIG4 are downregulated in patients with RPL owing to abnormal RNA degradation and dysregulated miRNA expression. LIG1 and LIG4 downregulation might contribute to the pathophysiological processes of RPL by increasing DNA damages.

Multicenter feasibility study to assess external quality panels for molecular diagnostics for tuberculosis in China.

The roll-out of molecular diagnostic tools continues to be the most important shift in the tuberculosis diagnostic landscape. The aim of this study was to develop a novel external quality assessment (EQA) panels for molecular TB diagnostics. In addition, we also assessed the performance of the laboratories with the EQA panels in China. Dried Mycobacterium tuberculosis (MTB) DNA in the chelex resin was designed as part of an EQA program. The storage of genomic DNA in the chelex resin layer had no effect on the stability of genomic DNA, even after 12 weeks of storage. Seventy-one laboratories have participated in EQA of molecular diagnostics for TB diagnosis in 2018. GeneXpert (74.6%, 53/71) was the most predominant molecular method, followed by GeneChip (32.3%, 23/71), MeltPro (22.5%, 16/71), and TB-LAMP (7.0%, 5/71). Out of 105 EQA panels, 103 EQA results (98.1%) achieved perfect scores, whereas the other two (1.9%) had satisfactory scores. There were a total of two false-negative results reported from two laboratories with local LAMP, respectively. In conclusion, we firstly develop feasible EQA panels for molecular diagnostics for tuberculosis in China. Our data demonstrate that a majority of participating laboratories are able to produce perfect results with molecular diagnostics in China, giving us important hints for the implementation of molecular diagnostics.

Exposure to low Earth orbit of an extreme-tolerant cyanobacterium as a contribution to lunar astrobiology activities

AbstractBy investigating the survival and the biomarker detectability of a rock-inhabiting cyanobacterium, Chroococcidiopsis sp. CCMEE 029, the BIOMEX space experiment might contribute to a future exploitation of the Moon as a test-bed for key astrobiology tasks such as the testing of life-detection technologies and the study of life in space. Post-flight analyses demonstrated that the mixing of dried cells with sandstone and a lunar regolith simulant provided protection against space UV radiation. During the space exposure, dried cells not mixed with minerals were killed by 2.05 × 102 kJ m−2 of UV radiation, while cells mixed with sandstone or lunar regolith survived 1.59 × 102 and 1.79 × 102 kJ m−2, respectively. No differences in survival occurred among cells mixed and not mixed with minerals and exposed to space conditions in the dark; this finding suggests that space vacuum and 0.5 Gy of ionizing radiation did not impair the cells’ presence in space. The genomic DNA of dead cells was severely damaged but still detectable with PCR amplification of a short target, thus suggesting that short sequences should be targeted in a PCR-based approach when searching for traces of life. The enhanced stability of genomic DNA of dried cells mixed with minerals and exposed to space indicates that DNA might still be detectable after prolonged periods, possibly up to millions of years in microbes shielded by minerals. Overall, the BIOMEX results contribute to future experiments regarding the exposure of cells and their biomarkers to deep space conditions in order to further test the lithopanspermia hypothesis, the biomarker stability and the microbial endurance, with implications for planetary protection and to determine if the Moon has been contaminated during past human missions.

De novo generation of a functional human thymus from induced pluripotent stem cells

A proper functional thymus is required for generation of T cell–mediated immunity. This is dramatically illustrated by patients lacking a thymus, such as children with complete DiGeorge syndrome, which is fatal if left untreated.1-3 Therapeutic options for such patients are limited and confined to transplantation of small fragments from allogeneic neonatal thymi.

Removal of antibiotics, antibiotic-resistant bacteria and their associated genes by graphene-based TiO2 composite photocatalysts under solar radiation in urban wastewaters

The present work investigated: (i) the removal of the antibiotics sulfamethoxazole (SMX), erythromycin (ERY) and clarithromycin (CLA); (ii) the inactivation of the total and antibiotic-resistant E. coli along with their regrowth potential after treatment; (iii) the removal of the total genomic DNA content; and (iv) the removal of selected antibiotic resistance genes (ARGs), namely sul1, ampC, ermB, mecA, as well as species-specific sequences, namely ecfX for Pseudomonas aeruginosa and enterococci-specific 23S rRNA, by graphene-based TiO2 composite photocatalysts under solar radiation, in real urban wastewaters. TiO2-reduced graphene oxide (TiO2-rGO) composite photocatalysts were synthesized by two ex-situ synthesis methods, namely hydrothermal (HD) treatment and photocatalytic (PH) treatment, starting from graphene oxide and Aeroxide P25 TiO2, and were characterized with various techniques, such as XRD, FT-IR, Raman, XPS, SEM and surface area (BET) analyses. The potential of the synthesized TiO2-rGO composites for the removal of the abovementioned antibiotic-related microcontaminants was compared to the efficiency shown by pristine Aeroxide P25 TiO2 under simulated solar radiation, in real urban wastewater effluents treated by a membrane bioreactor. The results showed that TiO2-rGO-PH was more efficient in the photocatalytic degradation of ERY (84±2%) and CLA (86±5%), while degradation of SMX (87±4%) was found to be slightly higher with Aeroxide P25 TiO2. It was also demonstrated that more than 180min of treatment were satisfactory for the complete inactivation and complete absence of post-treatment regrowth of E. coli bacteria (<LOD) even 24h after the end of the treatment, for all examined photocatalytic materials. The least amount of regrowth at all experimental times was observed in the presence of TiO2-rGO-HD. Moreover, the synthesized graphene-based photocatalysts successfully removed ampC and significantly reduced ecfX abundance of Pseudomonas aeruginosa, but sul1, ermB and 23S rRNA for enterococci sequences were found to be persistent throughout treatment with all catalyst types. Finally, the total DNA concentration remained stable throughout the photocatalytic treatment (4.2–4.8ngμL−1), indicating the high total genomic DNA stability in treated wastewater and its resistance to photocatalytic treatment.

Within-Day Baseline Variation in Salivary Biomarkers in Healthy Men.

Saliva is an easily accessible sample and offers practical and noninvasive biomarker solutions as an alternative to blood and urine-based diagnostics. Saliva contains a plethora of biomolecules such as nucleic acids, hormones, proteins, and electrolytes. On the other hand, little is known on the extent to which the biomolecules in saliva vary over time within a given person. This baseline information is crucial for future development of robust saliva-based diagnostics. We have collected unstimulated whole mouth saliva from 20 healthy young men at four times during the day, including before and after a meal. We measured the salivary cortisol, testosterone, C-reactive protein (CRP), stability of genomic DNA (gDNA) and DNA methylation levels of APC, P16INK4a, and PCQAP in these samples. We found that the salivary CRP, DNA methylation, and CD44 gDNA levels did not vary significantly across four time points (p > 0.05) while the salivary cortisol and testosterone levels significantly varied from the morning collection to the afternoon collection (p < 0.05). Furthermore, salivary cortisol levels were significantly affected by eating (p < 0.05). Our study offers a within-person baseline temporal assessment of several clinically relevant biomolecules and diagnostics, and suggests that salivary cortisol and testosterone levels vary over time in a given day whereas CRP and DNA methylation of tumor suppressor genes and CD44 amplification are stable throughout the day. Future research and clinical applications of salivary biomarkers and diagnostics should take into consideration their temporal variations.

Structural Studies of RNases H2 as an Example of Crystal Structure Determination of Protein-Nucleic Acid Complexes.

RNases H2 are nucleases that cleave nucleic acids that comprise both RNA and DNA. They specifically recognize and cleave junctions between RNA and DNA using an intricate mechanism that involves substrate-assisted catalysis. Archaeal and eukaryotic RNases H2 also cleave the RNA strands of RNA/DNA hybrids. RNases H2 use their activity to maintain the integrity of genetic information. Particularly important is their ability to initiate the removal of single ribonucleotides from genomic DNA. Single ribonucleotides are very common in replicating cells and pose a serious threat to the stability of genomic DNA. The only known pathway for the error-free removal of single ribonucleotides begins with their recognition and cleavage by RNases H2. The importance of these enzymes is further underscored by the fact that mutations in the human enzyme lead to a severe autoimmune disease, Aicardi-Goutières syndrome. This review summarizes methods for the overproduction and purification of bacterial and human RNases H2. We also describe methods for testing the enzymatic activity of these nucleases and their crystallization both in unliganded form and in complex with nucleic acid substrates. We use these studies to describe general principles of the crystallization and structure determination of protein-nucleic acid complexes, particularly for nucleases. As illustrated by the structural studies of RNases H2, such complex structures can reveal intricate and fascinating aspects of the molecular mechanisms of nucleic acid enzymes.

TET2-mediated 5-hydroxymethylcytosine induces genetic instability and mutagenesis.

The family of Ten-Eleven Translocation (TET) proteins is implicated in the process of active DNA demethylation and thus in epigenetic regulation. TET 1, 2 and 3 proteins are oxygenases that can hydroxylate 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) and further oxidize 5-hmC into 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). The base excision repair (BER) pathway removes the resulting 5-fC and 5-caC bases paired with a guanine and replaces them with regular cytosine. The question arises whether active modification of 5-mC residues and their subsequent elimination could affect the genomic DNA stability. Here, we generated two inducible cell lines (Ba/F3-EPOR, and UT7) overexpressing wild-type or catalytically inactive human TET2 proteins. Wild-type TET2 induction resulted in an increased level of 5-hmC and a cell cycle defect in S phase associated with higher level of phosphorylated P53, chromosomal and centrosomal abnormalities. Furthermore, in a thymine-DNA glycosylase (Tdg) deficient context, the TET2-mediated increase of 5-hmC induces mutagenesis characterized by GC>AT transitions in CpG context suggesting a mutagenic potential of 5-hmC metabolites. Altogether, these data suggest that TET2 activity and the levels of 5-hmC and its derivatives should be tightly controlled to avoid genetic and chromosomal instabilities. Moreover, TET2-mediated active demethylation might be a very dangerous process if used to entirely demethylate the genome and might rather be used only at specific loci.

DNA Damage in Major Psychiatric Diseases

Human cells are exposed to exogenous insults and continuous production of different metabolites. These insults and unwanted metabolic products might interfere with the stability of genomic DNA. Recently, many studies have demonstrated that different psychiatric disorders show substantially high levels of oxidative DNA damage in the brain accompanied with morphological and functional alterations. It reveals that damaged genomic DNA may contribute to the pathophysiology of these mental illnesses. In this article, we review the roles of oxidative damage and reduced antioxidant ability in some vastly studied psychiatric disorders and emphasize the inclusion of treatment options involving DNA repair. In addition, while most currently used antidepressants are based on the manipulation of the neurotransmitter regulation in managing different mental abnormalities, they are able to prevent or reverse neurotoxin-induced DNA damage. Therefore, it may be plausible to target on genomic DNA alterations for psychiatric therapies, which is of pivotal importance for future antipsychiatric drug development.

Editorial: Maintenance of Genome Integrity: DNA Damage Sensing, Signaling, Repair, and Replication in Plants.

Editorial: Maintenance of Genome Integrity: DNA Damage Sensing, Signaling, Repair, and Replication in Plants.

Automation Highlights from the Literature

Automation Highlights from the Literature

Benzo(a)pyrene disrupts mouse preimplantation embryo development

To determine the effects of Benzo(a)pyrene (BaP) on the development of early preimplantation embryo by exposure to physiologic concentrations of BaP based on a previous report in human ovarian follicular fluid and serum. Zygotes were cultured in 5nM or 50nM BaP and then examined for development efficiency, embryo quality, and DNA damage. In addition, embryonic stem cells (ESCs) were used as a model to test the toxic effects of BaP on inner cell mass (ICM) of blastocysts. Laboratory. CD1 mice. Mouse zygotes and ESCs were cultured in medium with 5nM or 50nM BaP. The percentage (rate) of blastocyst development, reactive oxygen species level, and quality of embryos assessed by total cell number, cell apoptosis, Oct4- and Nanog-positive cell ratio, and DNA damage on genomic and telomeric DNA were compared between dimethyl sulfoxide control and BaP treatments. The BaP-treated zygotes exhibited significantly higher reactive oxygen species activity, which might lead to more cell apoptosis, low ratio of Nanog- or Oct4-positive ICM cells, and increasing DNA damage in both genomic and telomeric DNA in blastocysts. By using mouse ESCs derived from ICM cells as a model, we showed that pluripotent cells might also show serious DNA damage after a brief exposure to BaP. Our data show that BaP could seriously disrupt cell growth and genomic DNA stability and increase cell apoptosis in mouse preimplantation embryo development.