Interplay between genotoxic factors formaldehyde and UV-B exacerbates genome instability in Arabidopsis

Maintenance of genome stability is quintessential feature for all living organisms. The simplest aldehyde formaldehyde and UV-B radiation, two environmental toxic factors, cause DNA damage, affect genome stability, subsequently growth and development across kingdoms. However, the interrelationship of genotoxicity caused by formaldehyde and UV-B remains fragmented in plants. Here, we show that mutants lacking one aldehyde detoxifying enzyme, alcohol dehydrogenase 2 (ADH2, also named GSNOR/FALDH), are hypersensitive to low dosage UV-B radiation or UV-B radiation-mimetic chemical in seedling and root growth. The defects are not caused by the alteration of UV-B sensing, secondary metabolites flavonoid accumulation, or ROS accumulation, rather are UV-B-induced genotoxicity. Increased DNA damage response genes and comet assay tail, cell cycle arrest upon exposure to UV-B provide direct evidence for DNA damage in gsnor mutant. Pharmacological analyses show that the susceptibility to genotoxic stresses is caused by the increased DNA crosslink which results from the enhanced endogenous formaldehyde in gsnor while UV-B promotes the production of formaldehyde. This implies formaldehyde clearance through GSNOR plays a critical role in response to environmental genotoxic stress and interplay between formaldehyde and UV-B exacerbates genome instability.

Al-Tolerant Barley Mutant hvatr.g Shows the ATR-Regulated DNA Damage Response to Maleic Acid Hydrazide

ATR, a DNA damage signaling kinase, is required for cell cycle checkpoint regulation and detecting DNA damage caused by genotoxic factors including Al3+ ions. We analyzed the function of the HvATR gene in response to chemical clastogen-maleic acid hydrazide (MH). For this purpose, the Al-tolerant barley TILLING mutant hvatr.g was used. We described the effects of MH on the nuclear genome of hvatr.g mutant and its WT parent cv. “Sebastian”, showing that the genotoxic effect measured by TUNEL test and frequency of cells with micronuclei was much stronger in hvatr.g than in WT. MH caused a significant decrease in the mitotic activity of root cells in both genotypes, however this effect was significantly stronger in “Sebastian”. The impact of MH on the roots cell cycle, analyzed using flow cytometry, showed no differences between the mutant and WT.

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

Telomeres in Plants and Humans: Not So Different, Not So Similar

Parallel research on multiple model organisms shows that while some principles of telomere biology are conserved among all eukaryotic kingdoms, we also find some deviations that reflect different evolutionary paths and life strategies, which may have diversified after the establishment of telomerase as a primary mechanism for telomere maintenance. Much more than animals, plants have to cope with environmental stressors, including genotoxic factors, due to their sessile lifestyle. This is, in principle, made possible by an increased capacity and efficiency of the molecular systems ensuring maintenance of genome stability, as well as a higher tolerance to genome instability. Furthermore, plant ontogenesis differs from that of animals in which tissue differentiation and telomerase silencing occur during early embryonic development, and the “telomere clock” in somatic cells may act as a preventive measure against carcinogenesis. This does not happen in plants, where growth and ontogenesis occur through the serial division of apical meristems consisting of a small group of stem cells that generate a linear series of cells, which differentiate into an array of cell types that make a shoot and root. Flowers, as generative plant organs, initiate from the shoot apical meristem in mature plants which is incompatible with the human-like developmental telomere shortening. In this review, we discuss differences between human and plant telomere biology and the implications for aging, genome stability, and cell and organism survival. In particular, we provide a comprehensive comparative overview of telomere proteins acting in humans and in Arabidopsis thaliana model plant, and discuss distinct epigenetic features of telomeric chromatin in these species.

The results of interconnection of the evidence of professional exposure to genotoxic factors (regex) and cancer registry in the Czech Republic

The aim of this study is to analyze the genotoxic risks in the Moravian-Silesian Region in the Czech Republic and assess the significance of genotoxic factors in the etiology of cancer by bringing together the Registry of Occupational Exposure to Genotoxic Factors and the Cancer Registry and compare the rate of detected cancer in persons exposed to genotoxic factors via their work in the Moravian-Silesian Region with the occurrence of cancer in the population of the Czech Republic. The results show: (a) For the monitored group (748 person) for the period 1996–2008, according to gender, was no statistically significant difference in the incidence of oncological diseases compared to the population of the Czech Republic. (b) But statistically significant difference was found in the cases of oncological diseases in groups according to % AB.C. using the Cytogenetic analysis of human peripheral lymphocytes (CAPL). The highest incidence was in the group with a higher incidence of % AB.C. High values of % AB.C. may predict the development of oncological diseases.

Assessment of chromosome instability in geese (Anser anser)

Wójcik, E. and Smalec, E. 2012. Assessment of chromosome instability in geese ( Anser anser ). Can. J. Anim. Sci. 92: 49–57. The basic test applied in the research of chromosome instability is the test of sister chromatid exchange (SCE). It makes it possible to identify single-and double-strand DNA damage caused by genotoxic factors and those that disrupt DNA damage repair mechanisms. Fragile sites in chromosomes can be found in all organisms. They are chromosome sites showing susceptibility to breakages and discontinuities in specific conditions of cell culture and also following induction with chemical substances. Chromosome instability of Anser anser geese was assessed in the research, focussing on sister chromatid exchange and the identification of fragile sites. The mean SCE/cell was 4.75±1.00. Most SCEs were identified in the proximal part of the chromosomes. Fragile sites were also identified in the chromosomes during the research. Altogether, 138 breakages were observed in the chromosomes. Apart from identifying chromosome damage, the particular instances of damage were located in the chromosomes.

Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics

Haploid male germ cells package their DNA into a volume that is typically 10% or less that of a somatic cell nucleus. To achieve this remarkable level of compaction, spermatozoa replace most of their histones with smaller, highly basic arginine and (in eutherians) cysteine rich protamines. One reason for such a high level of compaction is that it may help optimise nuclear shape and hence support the gametes' swimming ability for the long journey across the female reproductive tract to the oocyte. Super-compaction of the genome may confer additional protection from the effects of genotoxic factors. However, many species including the human retain a fraction of their chromatin in the more relaxed nucleosomal configuration that appears to run counter to the ergonomic, toroidal and repackaging of sperm DNA. Recent research suggests that the composition of this ‘residual’ nucleosomal compartment, a generally overlooked feature of the male gamete, is far more significant and important than previously thought. In this respect, the transport and incorporation of modified paternal histones by the spermatozoon to the zygote has been demonstrated and indicates another potential paternal effect in the epigenetic reprogramming of the zygote following fertilisation that is independent of imprinting status. In this review, the most recent research into mammalian spermatozoal chromatin composition is discussed alongside evidence for conserved, non-randomly located nucleosomal domains in spermatozoal nuclei, all supporting the hypothesis that the spermatozoon delivers a novel epigenetic signature to the egg that may be crucial for normal development. We also provide some thoughts on why this signature may be required in early embryogenesis.