genome damage
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2024 ◽  
Vol 84 ◽  
Author(s):  
R. M. Santos ◽  
A. C. Petry ◽  
V. L. Sousa ◽  
H. O. Souza ◽  
A. Azevedo ◽  
...  

Abstract Petroleum water soluble fraction (WSF) impairs organisms, but damages may vary among cell and tissue levels. The aim of the present study was to evaluate the acute (24 h, 48 h, 72 h) and subchronic effects (36 days) of WSF (0%, 25% and 100%) in juveniles of the Neotropical top predator fish Hoplias aff. malabaricus. The effects of WSF were evaluated at a molecular level using the comet assay and micronucleus test for genome damage; and at a morphological level through histological identification of liver pathologic lesions. In both acute and subchronic exposure we found low levels of DNA damage (< 10% of comet tail) and non-significant frequency of micronucleus in WSF exposed fish. The most significant liver lesions in WSF exposed fish were fatty vacuolization, hypertrophy and focal necrosis. Since these tissue injuries were progressive and persistent, their irreversibility may negatively affect fish recruitment, even in a such resistant top predator.


Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1882
Author(s):  
Delisa E. Clay ◽  
Donald T. Fox

Genome damage is a threat to all organisms. To respond to such damage, DNA damage responses (DDRs) lead to cell cycle arrest, DNA repair, and cell death. Many DDR components are highly conserved, whereas others have adapted to specific organismal needs. Immense progress in this field has been driven by model genetic organism research. This review has two main purposes. First, we provide a survey of model organism-based efforts to study DDRs. Second, we highlight how model organism study has contributed to understanding how specific DDRs are influenced by cell cycle stage. We also look forward, with a discussion of how future study can be expanded beyond typical model genetic organisms to further illuminate how the genome is protected.


2021 ◽  
Vol 11 ◽  
Author(s):  
Angeles Carlos-Reyes ◽  
Marcos A. Muñiz-Lino ◽  
Susana Romero-Garcia ◽  
César López-Camarillo ◽  
Olga N. Hernández-de la Cruz

Radiation therapy has been used worldwide for many decades as a therapeutic regimen for the treatment of different types of cancer. Just over 50% of cancer patients are treated with radiotherapy alone or with other types of antitumor therapy. Radiation can induce different types of cell damage: directly, it can induce DNA single- and double-strand breaks; indirectly, it can induce the formation of free radicals, which can interact with different components of cells, including the genome, promoting structural alterations. During treatment, radiosensitive tumor cells decrease their rate of cell proliferation through cell cycle arrest stimulated by DNA damage. Then, DNA repair mechanisms are turned on to alleviate the damage, but cell death mechanisms are activated if damage persists and cannot be repaired. Interestingly, some cells can evade apoptosis because genome damage triggers the cellular overactivation of some DNA repair pathways. Additionally, some surviving cells exposed to radiation may have alterations in the expression of tumor suppressor genes and oncogenes, enhancing different hallmarks of cancer, such as migration, invasion, and metastasis. The activation of these genetic pathways and other epigenetic and structural cellular changes in the irradiated cells and extracellular factors, such as the tumor microenvironment, is crucial in developing tumor radioresistance. The tumor microenvironment is largely responsible for the poor efficacy of antitumor therapy, tumor relapse, and poor prognosis observed in some patients. In this review, we describe strategies that tumor cells use to respond to radiation stress, adapt, and proliferate after radiotherapy, promoting the appearance of tumor radioresistance. Also, we discuss the clinical impact of radioresistance in patient outcomes. Knowledge of such cellular strategies could help the development of new clinical interventions, increasing the radiosensitization of tumor cells, improving the effectiveness of these therapies, and increasing the survival of patients.


2021 ◽  
Author(s):  
E. D. Baranova ◽  
V. G. Druzhinin ◽  
L. V. Matskova ◽  
P. S. Demenkov ◽  
V. P . Volobaev ◽  
...  

Abstract Recent findings indicate that the microbiome can have a significant impact on the development of lung cancer by inducing inflammatory responses, causing dysbiosis and generating genome damage. The aim of this study was to search for bacterial markers of squamous cell carcinoma (LUSC). In the study, the taxonomic composition of the sputum microbiome of 40 men with untreated LUSC was compared with 40 healthy controls. Next Generation sequencing of bacterial 16S rRNA genes was used to determine the taxonomic composition of the respiratory microbiome. There was no differences in alpha diversity between the LUSC and control groups. Meanwhile, differences in the structure of bacterial communities (β diversity) among patients and controls differed significantly in sputum samples (pseudo-F = 1.65; p = 0.026). Only Streptococcus, Bacillus, Gemella and Haemophilus were found to be significantly increased in patients with LUSC compared to the control subjects, while 19 bacterial genera were significantly reduced, indicating a decrease in beta diversity in the microbiome of patients with LUSC. From our study, Streptococcus (Streptococcus agalactiae) emerges as the most likely LUSC biomarker, but more research is needed to confirm this assumption.


2021 ◽  
Vol 43 (3) ◽  
pp. 1529-1547
Author(s):  
Lixiong Peng ◽  
Jiang Chang ◽  
Xilin Liu ◽  
Shiying Lu ◽  
Honglin Ren ◽  
...  

Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.


2021 ◽  
Vol 9 (10) ◽  
pp. 1088
Author(s):  
Andrey Alexandrovich Mazur ◽  
Viktor Pavlovich Chelomin ◽  
Elena Vladimirovna Zhuravel ◽  
Sergey Petrovich Kukla ◽  
Valentina Vladimirovna Slobodskova ◽  
...  

Microplastic pollution appears to be one of the major environmental problems in the world today, and researchers have been paying special attention to the study of the impact of microplastics on biota. In this article, we studied the short-term effects of polystyrene micro-spheres on genome integrity using the gametes of the Scaphechinus mirabilis sand dollar with the comet assay method. This highly sensitive method allowed us to identify the level of genome damage in both gametes before and after short-term exposure to PS microparticles. It was shown that primary polystyrene microspheres at concentrations of 104, 105, and 106 particles/L had a genotoxic effect during short-term exposure to the sperm of the sand dollar S. mirabilis, which was expressed as a significant increase in sperm DNA damage. The highest percentage of DNA damage (more than 20%) was detected in spermatozoa exposed for 1 h in water containing 105 microspheres of plastic per 1 L. Additionally, at all concentrations of microplastic studied in the experiment, the genetic damage index (GDI) values in spermatozoa exceeded the control level. However, regardless of the level of DNA damage, spermatozoa retained the ability to fertilise eggs with up to 97% efficiency. We must acknowledge that the genotoxic property of microplastic against sperm to some extent predicts the development of long-term adverse effects of environmental significance.


Mutagenesis ◽  
2021 ◽  
Author(s):  
Consuelo Micheli ◽  
Alice Parma ◽  
Chiara Tani ◽  
Domenica Di Bello ◽  
Aurora Falaschi ◽  
...  

Abstract Immunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY 581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterize SLE and UCTD, aiming to improve the treatment plan and the quality of the patients’ life.


2021 ◽  
Author(s):  
J.A. Black ◽  
K. Crouch ◽  
E. Briggs ◽  
L. Lemgruber ◽  
C. Lapsely ◽  
...  

AbstractInheritance of aberrant chromosomes can compromise genome integrity and affect cellular fitness. In eukaryotes, surveillance pathways and cell cycle checkpoints monitor for aberrant DNA transmission and the ATR kinase, a regulator of the DNA damage response, plays a pivotal role. Prior work revealed that ATR acts during antigenic variation in Trypanosoma brucei mammal-infective life cycle forms and that its loss is lethal, but how widely ATR operates in genome maintenance is largely unknown. Here, we show that after prolonged ATR depletion by RNAi T. brucei continues to synthesise DNA and enters new rounds of cell division, despite increased genome damage. Furthermore, we detect defective chromosome segregation, ‘micronuclei’ formation and disruption of the nuclear architecture. RNA-seq revealed that loss of ATR affects the expression of nearly half the genes in the genome, including both RNA Polymerase I and II transcription. Using ChIP-seq of yH2A and DRIP-seq, we reveal overlapping signals for genome damage and R-loops after ATR depletion in all intergenic regions. In addition, we report reduced R-loop levels and accumulation of yH2A signal within centromeres. Together, our data indicates widespread roles of ATR in T. brucei, including differing roles in R-loop homeostasis during multigene transcription and in chromosome segregation.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009735
Author(s):  
Weier Guo ◽  
Luca Comai ◽  
Isabelle M. Henry

Chromoanagenesis is a genomic catastrophe that results in chromosomal shattering and reassembly. These extreme single chromosome events were first identified in cancer, and have since been observed in other systems, but have so far only been formally documented in plants in the context of haploid induction crosses. The frequency, origins, consequences, and evolutionary impact of such major chromosomal remodeling in other situations remain obscure. Here, we demonstrate the occurrence of chromoanagenesis in poplar (Populus sp.) trees produced from gamma-irradiated pollen. Specifically, in this population of siblings carrying indel mutations, two individuals exhibited highly frequent copy number variation (CNV) clustered on a single chromosome, one of the hallmarks of chromoanagenesis. Using short-read sequencing, we confirmed the presence of clustered segmental rearrangement. Independently, we identified and validated novel DNA junctions and confirmed that they were clustered and corresponded to these rearrangements. Our reconstruction of the novel sequences suggests that the chromosomal segments have reorganized randomly to produce a novel rearranged chromosome but that two different mechanisms might be at play. Our results indicate that gamma irradiation can trigger chromoanagenesis, suggesting that this may also occur when natural or induced mutagens cause DNA breaks. We further demonstrate that such events can be tolerated in poplar, and even replicated clonally, providing an attractive system for more in-depth investigations of their consequences.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1938
Author(s):  
Vanessa Khemici ◽  
Marc Prudhomme ◽  
Patrice Polard

Cells respond to genome damage by inducing restorative programs, typified by the SOS response of Escherichia coli. Streptococcus pneumoniae (the pneumococcus), with no equivalent to the SOS system, induces the genetic program of competence in response to many types of stress, including genotoxic drugs. The pneumococcal competence regulon is controlled by the origin-proximal, auto-inducible comCDE operon. It was previously proposed that replication stress induces competence through continued initiation of replication in cells with arrested forks, thereby increasing the relative comCDE gene dosage and expression and accelerating the onset of competence. We have further investigated competence induction by genome stress. We find that absence of RecA recombinase stimulates competence induction, in contrast to SOS response, and that double-strand break repair (RexB) and gap repair (RecO, RecR) initiation effectors confer a similar effect, implying that recombinational repair removes competence induction signals. Failure of replication forks provoked by titrating PolC polymerase with the base analogue HPUra, over-supplying DnaA initiator, or under-supplying DnaE polymerase or DnaC helicase stimulated competence induction. This induction was not correlated with concurrent changes in origin-proximal gene dosage. Our results point to arrested and unrepaired replication forks, rather than increased comCDE dosage, as a basic trigger of pneumococcal competence.


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