scholarly journals Consequences of Genomic DNA Mono-Ribonucleotides for Chromosomal Stability

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1006-1006
Author(s):  
Tavia Roache
Keyword(s):  
Messenger Rna ◽  
Genomic Dna ◽  
Cellular Response ◽  
Excision Repair ◽  
Access Point ◽  
Building Blocks ◽  
Negative Consequences ◽  
Negative Effects ◽  
Topoisomerase 1 ◽  
Rnase H2

Abstract Mono-ribonucleotides are building blocks for polynucleotide RNA chains (e.g., messenger RNA), but if mis-incorporated into duplex DNA can cause mutagenesis and chromosomal instability. During DNA synthesis by Pol γ, remnants of unremoved RNA primers contribute to elevated mono-ribonucleotide triphosphates resulting in nucleotide pool imbalance, ultimately favoring mis-incorporated ribonucleotides during replication. Moreover, although polymerases generally replicate DNA with high fidelity, the steric gate occasionally allows a mis-incorporated ribonucleotide. Thus, a mono-ribonucleotide is one of the most abundant lesions in genomic DNA of eukaryotes. If unremoved from double-stranded DNA, the ribonucleotide exerts negative effects on replication, transcription, and genomic maintenance, with lasting effects on cellular homeostasis. Even a single ribonucleotide in telomeric DNA comprises shelterin binding and telomere capping causing vulnerability to spontaneous hydrolysis which potentiates telomere shortening. Consistent with this, a ribonucleotide positioned in double-helical DNA alters its structure by torsinally distorting the sugar-phosphate backbone. Fortunately, cellular response and repair pathways exist to help cells cope with mis-incorporated mono-ribonucleotides. The Ribonucleotide Excision Repair (RER) or a Topoisomerase 1 (Top1)-mediated pathway remove embedded ribonucleotides. For RER, RNase H2 incises 5’ of a mono-ribonucleotide, creating an access point for its removal. If cells are deficient in RNase H2, Top1 initiates removal of the ribonucleotide. However, Top1 is less accurate than RNase H2, which can lead to mutagenesis. Studying the mechanisms in which ribonucleotides are incorporated into DNA or further metabolized should provide insight to their negative consequences for chromosomal integrity, cancer, and auto-immune disease attributed to a genetic deficiency of RNase H2.

scholarly journals High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase

2020 ◽  
Vol 48 (8) ◽  
pp. 4274-4297 ◽  
Author(s):  
Susana M Cerritelli ◽  
Jaime Iranzo ◽  
Sushma Sharma ◽  
Andrei Chabes ◽  
Robert J Crouch ◽  
...  
Keyword(s):  
Ribonucleotide Reductase ◽  
Genomic Dna ◽  
Genome Instability ◽  
Excision Repair ◽  
Topoisomerase 1 ◽  
Growth Defects ◽  
Rnase H2 ◽  
Cell Lethality ◽  
Severe Growth ◽  
Excessive Accumulation

Abstract Cellular levels of ribonucleoside triphosphates (rNTPs) are much higher than those of deoxyribonucleoside triphosphates (dNTPs), thereby influencing the frequency of incorporation of ribonucleoside monophosphates (rNMPs) by DNA polymerases (Pol) into DNA. RNase H2-initiated ribonucleotide excision repair (RER) efficiently removes single rNMPs in genomic DNA. However, processing of rNMPs by Topoisomerase 1 (Top1) in absence of RER induces mutations and genome instability. Here, we greatly increased the abundance of genomic rNMPs in Saccharomyces cerevisiae by depleting Rnr1, the major subunit of ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides. We found that in strains that are depleted of Rnr1, RER-deficient, and harbor an rNTP-permissive replicative Pol mutant, excessive accumulation of single genomic rNMPs severely compromised growth, but this was reversed in absence of Top1. Thus, under Rnr1 depletion, limited dNTP pools slow DNA synthesis by replicative Pols and provoke the incorporation of high levels of rNMPs in genomic DNA. If a threshold of single genomic rNMPs is exceeded in absence of RER and presence of limited dNTP pools, Top1-mediated genome instability leads to severe growth defects. Finally, we provide evidence showing that accumulation of RNA/DNA hybrids in absence of RNase H1 and RNase H2 leads to cell lethality under Rnr1 depletion.

scholarly journals Both R-loop removal and ribonucleotide excision repair activities of RNase H2 contribute substantially to chromosome stability

DNA Repair ◽  
2017 ◽  
Vol 52 ◽  
pp. 110-114 ◽  
Author(s):  
Deborah A. Cornelio ◽  
Hailey N.C. Sedam ◽  
Jessica A. Ferrarezi ◽  
Nadia M.V. Sampaio ◽  
Juan Lucas Argueso
Keyword(s):  
Excision Repair ◽  
Chromosome Stability ◽  
Rnase H2

Impact of the Global Financial Crisis on IT Sector. The Case of Greece

2022 ◽  
Vol 9 (1) ◽  
pp. 0-0
Keyword(s):  
Global Financial Crisis ◽  
Extended Period ◽  
Early Years ◽  
Negative Consequences ◽  
Negative Effects ◽  
Innovation Development ◽  
Negative Effect ◽  
Greek Economy ◽  
The Global Financial Crisis ◽  
The Impact

The impact of the Information and Technology (IT) sector on the countries’ innovation development has been recognized as crucial in prior and recent research studies. Moreover, firms’ innovativeness affects positively countries’ economies. Nevertheless, the global economic crisis of the last decade constituted a significant barrier to the development of country economies and had a negative effect on firms’ performance. Specifically, the negative consequences of the global crisis became harder for Southern Europe Countries. More specifically the Greek economy was suffered by an extended period of crisis with harder consequences than those of other European countries. The main purpose of this study was to examine the financial performance of Greek IT firms in the early years of crisis. Our findings have been relevant to those of previous studies which observed negative effects of the financial recession on firms profitability.

Unemployment Normalization: Its Effect on Mental Health During Various Stages of Unemployment

2018 ◽  
Vol 122 (5) ◽  
pp. 1600-1617 ◽  
Author(s):  
Steve Thill ◽  
Claude Houssemand ◽  
Anne Pignault
Keyword(s):  
Mental Health ◽  
General Health ◽  
Job Loss ◽  
First Year ◽  
Negative Consequences ◽  
Positive Perception ◽  
Negative Effects ◽  
Coping Process ◽  
Normalization Process

The negative effects of job loss on mental health have been thoroughly described in the literature. However, different fluctuations in mental health during the unemployment period have been noticed. We argue that a coping process takes place in this kind of situation. Therefore, in this study, we investigated the effect of the unemployment normalization process on mental health during various stages of unemployment. Participants ( N = 803) completed the General Health Questionaire-12 and the Unemployment Normalization Questionnaire. Results showed that a negative perception of unemployment had the greatest impact on mental health during the different phases of unemployment. Nevertheless, during the first year, having a positive perception counteracted these negative effects, and after 1 year, the unemployment norm took over the role of buffering against the negative effects on mental health. These results indicate that unemployment is still perceived as negative, but depending on the stage of unemployment, various coping strategies are used to buffer the negative consequences of unemployment.

scholarly journals Poaching vs. patrolling: effects on conservation of Cory’s Shearwater Calonectris diomedea borealis colonies

2011 ◽  
Vol 21 (3) ◽  
pp. 342-352 ◽  
Author(s):  
MARTA LOPEZ-DARIAS ◽  
JAVIER LUZARDO ◽  
RAFAEL MARTÍNEZ ◽  
DANIEL GONZÁLEZ ◽  
EDUARDO A. GARCÍA ◽  
...  
Keyword(s):  
Canary Islands ◽  
Breeding Success ◽  
Conservation Status ◽  
Negative Consequences ◽  
Negative Effects ◽  
Seabird Species ◽  
Cory’S Shearwater ◽  
Final Population ◽  
Calonectris Diomedea ◽  
Government Surveillance

SummaryNegative effects of poaching on seabird populations are not usually evaluated quantitatively when assessing seabird colony conservation status, nor are they generally considered a major concern. We demonstrate that poaching is still intense in the Canary Islands, and has negative consequences for the conservation of seabird colonies. We quantified the effects of poaching of Cory’s Shearwater fledglings on breeding success on different islands in the Canaries, comparing colonies that suffer from intense, medium, or no poaching. Poaching reduced the breeding success of affected colonies to almost a third, potentially causing the future extinction of the colony. Only colonies with intense wardening campaigns reached high values of reproductive success, showing that government surveillance in conjunction with volunteers from different NGOs is a very effective approach in reducing poaching. A population sensitivity analysis was also conducted to provide data on the factors that most affect the performance of the model. Although population growth and mean final population size varied with increases and decreases in mortality and carrying capacity, only harvesting resulted in a probability of 100% of extinction in 20–40 years. To promote seabird conservation in regions such as the Canary Islands, a core archipelago for seabird species in the Atlantic, poaching control should be elevated by society to a level of urgency, requiring dedicated funding and mobilisation of experts and volunteers to adequately address it through education, prevention and enforcement.

Measuring Outcomes in Alzheimer's Disease

1996 ◽  
Vol 8 (S1) ◽  
pp. 13-16 ◽  
Author(s):  
Rhonda J. V. Montgomery
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Behavioral Problems ◽  
Negative Consequences ◽  
Negative Effects ◽  
Target Individual ◽  
Measuring Outcomes ◽  
Study Designs ◽  
The Impact ◽  
Initial Target

The premise underlying the implementation of any intervention aimed at changing behavioral or other symptoms of Alzheimer's disease (AD) is that the change will be beneficial in some manner for the patient and the benefits will outweigh any negative consequences that may simultaneously result from the intervention. Consequently, the ultimate task of investigators studying the impact of proposed interventions is to identify and measure the benefit that stems from the intervention, as well as any negative effects. When interventions are intended to create organic changes, as is traditionally true with pharmacologic interventions, the identification of relevant outcomes is made relatively simple through indicators of organic functioning. However, when intended changes are behavioral, the identification of appropriate outcomes is far more complex. An individual's behavior ultimately has an impact on all the actors within his or her social setting, directly or indirectly. Furthermore, changes in an individual's behavior may have an impact on other persons in such a way that these secondary changes feed back to further influence the initial target individual. Hence, it is likely that the most appropriate study designs for assessing the impact of interventions aimed at behavioral problems will include multiple outcome measures for multiple actors.

scholarly journals hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Didier Boucher ◽  
Ruvini Kariawasam ◽  
Joshua Burgess ◽  
Adrian Gimenez ◽  
Tristan E. Ocampo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Response ◽  
Excision Repair ◽  
Protein A ◽  
Ultraviolet B ◽  
Repair System ◽  
Uvb Radiation ◽  
Exogenous Dna

AbstractMaintenance of genomic stability is critical to prevent diseases such as cancer. As such, eukaryotic cells have multiple pathways to efficiently detect, signal and repair DNA damage. One common form of exogenous DNA damage comes from ultraviolet B (UVB) radiation. UVB generates cyclobutane pyrimidine dimers (CPD) that must be rapidly detected and repaired to maintain the genetic code. The nucleotide excision repair (NER) pathway is the main repair system for this type of DNA damage. Here, we determined the role of the human Single-Stranded DNA Binding protein 2, hSSB2, in the response to UVB exposure. We demonstrate that hSSB2 levels increase in vitro and in vivo after UVB irradiation and that hSSB2 rapidly binds to chromatin. Depletion of hSSB2 results in significantly decreased Replication Protein A (RPA32) phosphorylation and impaired RPA32 localisation to the site of UV-induced DNA damage. Delayed recruitment of NER protein Xeroderma Pigmentosum group C (XPC) was also observed, leading to increased cellular sensitivity to UVB. Finally, hSSB2 was shown to have affinity for single-strand DNA containing a single CPD and for duplex DNA with a two-base mismatch mimicking a CPD moiety. Altogether our data demonstrate that hSSB2 is involved in the cellular response to UV exposure.

scholarly journals Legal protection of the Arctic environment related tourism activity

2020 ◽  
pp. 9-23
Author(s):  
Nikolai Kudelkin
Keyword(s):  
Legal Protection ◽  
Legal Regulation ◽  
The Arctic ◽  
Infrastructure Development ◽  
Negative Consequences ◽  
Negative Effects ◽  
Economic Sectors ◽  
Arctic Environment ◽  
Cruise Tourism ◽  
Tourism Activity

The Arctic continues to attract more and more tourists. In some of the Arctic regions, tourism in general and cruise tourism in particular is becoming one of the fastest growing economic sectors. However, aside from the economic benefit, the Arctic tourism poses a certain threat to the sensitive environment of the Arctic, which currently experiences constantly increasing pressure from economic activity and climate change. Major negative consequences of tourism activity include the pollution of territories and water zones, worry of animals, direct destruction of flora and fauna, loss of the places of habitat due to infrastructure development, etc. The listed facts underline relevance of the selected topic of research, as well as the need for legal protection of the Arctic environment from negative effects caused by tourism. Analysis is conducted on the current situation in the area of Arctic tourism, as well as the questions of Russia’s Arctic policy pertaining to tourism activity. A brief overview is provided to the international legal regulation in this sphere. The author concludes on the insufficiency of legal regulation in the area of Arctic tourism, and gives recommendations on the improvement of Russian legislation. It is noted that tourism is one of the few types of activities in the Arctic that sparks interests of multiple countries, and in which the acceptance of universal standards seems possible.

scholarly journals THE IMPACT OF THE COVID-19 PANDEMIC ON INDUSTRY 4.0 IN THE CONTEXT OF GLOBAL ECONOMIC DEVELOPMENT

InterConf ◽  
2021 ◽  
pp. 54-59
Author(s):  
Bohdana Hunko
Keyword(s):  
Economic Development ◽  
Industry 4.0 ◽  
Global Economy ◽  
Industrial Revolution ◽  
Negative Consequences ◽  
Negative Effects ◽  
Technology Industry ◽  
World Economic ◽  
The Impact

The paper analyzes the role of Industry 4.0 in the process of overcoming the global economy from the crisis situation associated with the total Covid-19 pandemic. The aspect of economic profitability of using the technologies of the fourth industrial revolution to improve world economic development in the context of the Covid-19 pandemic was also identified. The author identified the positive and negative consequences of the involvement of technology Industry 4.0, on the basis of which a number of recommendations for small and medium-sized businesses were formed in order to quickly overcome the negative effects of the crisis. Based on the work, the author formulated a number of trends and prospects for global economic development, taking into account the current conditions of the Covid-19 pandemic.

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