scholarly journals Role of 53BP1 in end protection and DNA synthesis at DNA breaks

2021 ◽  
Author(s):  
Jacob Paiano ◽  
Nicholas Zolnerowich ◽  
Wei Wu ◽  
Raphael Pavani ◽  
Chen Wang ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Nuclease Activity ◽  
Extent Of Resection ◽  
Strand Break ◽  
Dna Breaks ◽  
Initial Processing ◽  
The Relationship ◽  
Dna Ends ◽  
Insight Into

Double-strand break (DSB) repair choice is greatly influenced by the initial processing of DNA ends. 53BP1 limits the formation of recombinogenic single-strand DNA (ssDNA) in BRCA1-deficient cells, leading to defects in homologous recombination (HR). However, the exact mechanisms by which 53BP1 inhibits DSB resection remain unclear. Previous studies have identified two potential pathways: protection against DNA2/EXO1 exonucleases presumably through the Shieldin (SHLD) complex binding to ssDNA, and localized DNA synthesis through the CTC1-STN1-TEN1 (CST) and DNA polymerase α (Polα) to counteract resection. Using a combinatorial approach of END-seq, SAR-seq, and RPA ChIP-seq, we directly assessed the extent of resection, DNA synthesis, and ssDNA, respectively, at restriction enzyme-induced DSBs. We show that, in the presence of 53BP1, Polα-dependent DNA synthesis reduces the fraction of resected DSBs and the resection lengths in G0/G1, supporting a previous model that fill-in synthesis can limit the extent of resection. However, in the absence of 53BP1, Polα activity is sustained on ssDNA yet does not substantially counter resection. In contrast, EXO1 nuclease activity is essential for hyperresection in the absence of 53BP1. Thus, Polα-mediated fill-in partially limits resection in the presence of 53BP1 but cannot counter extensive hyperresection due to the loss of 53BP1 exonuclease blockade. These data provide the first nucleotide mapping of DNA synthesis at resected DSBs and provide insight into the relationship between fill-in polymerases and resection exonucleases.

scholarly journals Genetic Separation of Sae2 Nuclease Activity from Mre11 Nuclease Functions in Budding Yeast

2017 ◽  
Vol 37 (24) ◽  
Author(s):  
Sucheta Arora ◽  
Rajashree A. Deshpande ◽  
Martin Budd ◽  
Judy Campbell ◽  
America Revere ◽  
...  
Keyword(s):  
Nuclease Activity ◽  
Double Strand Breaks ◽  
Endonuclease Activity ◽  
Dna Double Strand Breaks ◽  
Dna Breaks ◽  
Content Type ◽  
Strand Breaks ◽  
Dna Ends

ABSTRACT Sae2 promotes the repair of DNA double-strand breaks in Saccharomyces cerevisiae. The role of Sae2 is linked to the Mre11/Rad50/Xrs2 (MRX) complex, which is important for the processing of DNA ends into single-stranded substrates for homologous recombination. Sae2 has intrinsic endonuclease activity, but the role of this activity has not been assessed independently from its functions in promoting Mre11 nuclease activity. Here we identify and characterize separation-of-function mutants that lack intrinsic nuclease activity or the ability to promote Mre11 endonucleolytic activity. We find that the ability of Sae2 to promote MRX nuclease functions is important for DNA damage survival, particularly in the absence of Dna2 nuclease activity. In contrast, Sae2 nuclease activity is essential for DNA repair when the Mre11 nuclease is compromised. Resection of DNA breaks is impaired when either Sae2 activity is blocked, suggesting roles for both Mre11 and Sae2 nuclease activities in promoting the processing of DNA ends in vivo. Finally, both activities of Sae2 are important for sporulation, indicating that the processing of meiotic breaks requires both Mre11 and Sae2 nuclease activities.

On Metaphysics and the Political: A Polemics of Reading Baudelaire in the 1930s

2019 ◽  
Vol 58 (2) ◽  
pp. 249-259
Author(s):  
Joseph Acquisto
Keyword(s):  
Twentieth Century ◽  
Political Crisis ◽  
The Political ◽  
Modern Poetry ◽  
Progressive Politics ◽  
The World ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

This essay examines a polemic between two Baudelaire critics of the 1930s, Jean Cassou and Benjamin Fondane, which centered on the relationship of poetry to progressive politics and metaphysics. I argue that a return to Baudelaire's poetry can yield insight into what seems like an impasse in Cassou and Fondane. Baudelaire provides the possibility of realigning metaphysics and politics so that poetry has the potential to become the space in which we can begin to think the two of them together, as opposed to seeing them in unresolvable tension. Or rather, the tension that Baudelaire animates between the two allows us a new way of thinking about the role of esthetics in moments of political crisis. We can in some ways see Baudelaire as responding, avant la lettre, to two of his early twentieth-century readers who correctly perceived his work as the space that breathes a new urgency into the questions of how modern poetry relates to the world from which it springs and in which it intervenes.

scholarly journals Designing for international law: The architecture of international organizations 1922–1952

2020 ◽  
pp. 1-22
Author(s):  
Miriam Bak McKenna
Keyword(s):  
New York ◽  
International Law ◽  
International Organizations ◽  
International Organization ◽  
International Labour Organization ◽  
The Relationship ◽  
Physical Manifestation ◽  
Insight Into ◽  
Do So

Abstract Situating itself in current debates over the international legal archive, this article delves into the material and conceptual implications of architecture for international law. To do so I trace the architectural developments of international law’s organizational and administrative spaces during the early to mid twentieth century. These architectural endeavours unfolded in three main stages: the years 1922–1926, during which the International Labour Organization (ILO) building, the first building exclusively designed for an international organization was constructed; the years 1927–1937 which saw the great polemic between modernist and classical architects over the building of the Palace of Nations; and the years 1947–1952, with the triumph of modernism, represented by the UN Headquarters in New York. These events provide an illuminating allegorical insight into the physical manifestation, modes of self-expression, and transformation of international law during this era, particularly the relationship between international law and the function and role of international organizations.

scholarly journals Insight into the Double-Edged Role of Ferroptosis in Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1790
Author(s):  
Lei Zhang ◽  
Ruohan Jia ◽  
Huizhen Li ◽  
Huarun Yu ◽  
Keke Ren ◽  
...  
Keyword(s):  
Cell Death ◽  
Digestive System ◽  
Kidney Injury ◽  
Oxygen Species ◽  
Disease Treatment ◽  
The Relationship ◽  
Insight Into ◽  
New Strategies ◽  
Research Hotspots

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.

Regulation of TRPV5 and TRPV6 by associated proteins

2006 ◽  
Vol 290 (6) ◽  
pp. F1295-F1302 ◽  
Author(s):  
Stan F. J. van de Graaf ◽  
Joost G. J. Hoenderop ◽  
René J. M. Bindels
Keyword(s):  
Molecular Mechanisms ◽  
Hormonal Control ◽  
Trp Channel ◽  
Intestinal Lumen ◽  
Blood Compartment ◽  
Associated Proteins ◽  
The Relationship ◽  
Insight Into ◽  
Prime Target

The epithelial Ca2+ channels TRPV5 and TRPV6 are the most Ca2+-selective members of the TRP channel superfamily. These channels are the prime target for hormonal control of the active Ca2+ flux from the urine space or intestinal lumen to the blood compartment. Insight into their regulation is, therefore, pivotal in our understanding of the (patho)physiology of Ca2+ homeostasis. The recent elucidation of TRPV5/6-associated proteins has provided new insight into the molecular mechanisms underlying the regulation of these channels. In this review, we describe the various means of TRPV5/6 regulation, the role of channel-associated proteins herein, and the relationship between both processes.

scholarly journals Hypoxia-inducible factor–1 and associated upstream and downstream proteins in the pathophysiology and management of glioblastoma

2014 ◽  
Vol 37 (6) ◽  
pp. E8 ◽  
Author(s):  
Matthew Womeldorff ◽  
David Gillespie ◽  
Randy L. Jensen
Keyword(s):  
Cellular Response ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Poor Patient ◽  
Growth Development ◽  
The Relationship ◽  
Insight Into ◽  
Upstream Regulators

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an exceptionally poor patient outcome despite aggressive therapy including surgery, radiation, and chemotherapy. This aggressive phenotype may be associated with intratumoral hypoxia, which probably plays a key role in GBM tumor growth, development, and angiogenesis. A key regulator of cellular response to hypoxia is the protein hypoxia-inducible factor–1 (HIF-1). An examination of upstream hypoxic and nonhypoxic regulation of HIF-1 as well as a review of the downstream HIF-1–regulated proteins may provide further insight into the role of this transcription factor in GBM pathophysiology. Recent insights into upstream regulators that intimately interact with HIF-1 could provide potential therapeutic targets for treatment of this tumor. The same is potentially true for HIF-1–mediated pathways of glycolysis-, angiogenesis-, and invasion-promoting proteins. Thus, an understanding of the relationship between HIF-1, its upstream protein regulators, and its downstream transcribed genes in GBM pathogenesis could provide future treatment options for the care of patients with these tumors.

The Investment Model: Its Antecedents and Predictors of Relationship Satisfaction

2020 ◽  
Vol 11 ◽  
Author(s):  
Kathleen A. Moore ◽  
Austin Campbell
Keyword(s):  
Relationship Satisfaction ◽  
Intimate Relationships ◽  
Investment Model ◽  
Knowing How ◽  
The Relationship ◽  
Insight Into

Abstract Intimate relationships are an integral part of our lives, but the rate of relationship breakups is high. We explored the role of the investment model and the traits that influence investments on relationship satisfaction among 146 volunteers (age M = 28.76 years, SD = 10.23). Relationship satisfaction was predicted by investments, which in turn were predicted by attachment, personality and love style. Clinicians working with individuals or couples with relationship issues may benefit from knowing how invested they are in the relationship and their love style. Insight into imbalances in these constructs between partners may be used to facilitate relationship satisfaction.

scholarly journals Religion, civil society and conflict: What is it that religion does for and to society?

2011 ◽  
Vol 67 (3) ◽  
Author(s):  
Jaco Beyers
Keyword(s):  
Civil Society ◽  
Sociology Of Religion ◽  
Multiple Realities ◽  
Moral Discernment ◽  
Sense Of Reality ◽  
Definition Of ◽  
Role Of Religion ◽  
The Relationship ◽  
Insight Into

Human consciousness instinctively tries to make sense of reality. Different human interpretations of reality lead to a world consisting of multiple realities. Conflict occurs when differing realities (worldviews) encounter one another. Worldviews are socially created and determine human behaviour and, as such, most often find expression in religion. The discussion of conflict and the role of religion in civil society take place within the discourse of the sociology of religion. Religion is socially determined. Peter Berger’s insight into the sociology of religion therefore plays an important role in establishing the relationship between religion and civil society as one that takes on different forms. Thus, a clear definition of both civil society and religion was needed to understand the nature of these relationships. The role of religion in civil society with regard to the presence of conflict in society was further investigated in this article. The conditions under which conflict in society occurs were discussed, as were the conditions for tolerance in society, for religion ultimately becomes the provider of moral discernment when conflict occurs in civil society.

Social Media Use Among Olympians and Sport Journalists in Hungary

2020 ◽  
Vol 13 (2) ◽  
pp. 181-199
Author(s):  
Agnes Kovacs ◽  
Tamas Doczi ◽  
Dunja Antunovic
Keyword(s):  
Social Media ◽  
Media Use ◽  
Social Media Use ◽  
The World ◽  
Social Media Platforms ◽  
The Media ◽  
Hungarian Case ◽  
The Relationship ◽  
Insight Into

The Olympic Games are among the most followed events in the world, so athletes who participate there are exceptionally interesting for the media. This research investigated Olympians’ social media use, sport journalists’ attitudes about Olympians’ social media use, and the role of social media in the relationship between Olympians and sport journalists in Hungary. The findings suggest that most Hungarian Olympians do not think that being on social media is an exceptionally key issue in their life, and a significant portion of them do not have public social media pages. However, sport journalists would like to see more information about athletes on social media platforms. The Hungarian case offers not only a general understanding of the athlete–journalist relationship, and the role of social media in it, but also insight into the specific features of the phenomenon in a state-supported, hybrid sport economy.

Feeding ecology of the non-indigenous fish Hypomesus nipponensis in Lake Ulungur, China: insight into the relationship between its introduction and the collapse of the native Eurasian perch population

2013 ◽  
Vol 64 (6) ◽  
pp. 549
Author(s):  
Xiaoyu Zhou ◽  
Zhongjun Hu ◽  
Qigen Liu ◽  
Lili Yang ◽  
Yubo Wang
Keyword(s):  
Feeding Ecology ◽  
Important Food ◽  
Eurasian Perch ◽  
Chironomid Larvae ◽  
Feeding Spectrum ◽  
Index Of Relative Importance ◽  
The Relationship ◽  
Japanese Smelt ◽  
Insight Into

Studies of feeding ecology are essential in gaining an understanding of how established non-indigenous fish species interact with the invaded communities. In the present study, we investigated the composition and seasonal variation in the diet of the introduced Japanese smelt Hypomesus nipponensis, a small planktivorous fish, in Lake Ulungur, China. The objective was to examine the ecological role of this established non-indigenous smelt through the analysis of its diet, which might give more insight into the relationship between its introduction and the collapse of the native Eurasian perch population. Results showed that the Japanese smelt had a broader feeding spectrum than had been previously reported. Of 10 taxonomic or ecological categories of food, cladocerans (54.70%) and rotifers (15.39%) were the most important food items in terms of the index of relative importance (IRI), whereas surface food and chironomid larvae were the most important by weight. Although cladocerans were consistently the most important food, rotifers and copepods, together with surface food and chironomid larvae, substituted when cladocerans were scarcer. Because both rotifers and chironomid larvae are important food of larval and young perch, introduction of Japanese smelt into the lake might be responsible for the collapse of the perch population because of the suppression of rotifers and chironomid larvae in spring through seasonal predation.

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