Repair of DNA Strand Breaks in a Minichromosome In Vivo: Kinetics, Modeling, and Effects of Inhibitors

Kumala, Sławomir; Fujarewicz, Krzysztof; Dheekollu, Jayaraju; Rzeszowska-Wolny, Joanna; Hancock, Ronald

doi:10.1371/journal.pone.0052966

Cited by 8 publications

(13 citation statements)

References 99 publications

(106 reference statements)

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“…To study ionizing radiation-induced DNA damage and repair in vivo we performed experiments using the circular 172 kb long Epstein-Barr virus minichromosome which is stably maintained in ∼50 copies in cells of the Burkitt's lymphomaderived Raji cell line. This minichromosome has the same nucleosomal structure as human chromosomes and its different topological forms and fragments appearing after irradiation can be easily observed and quantitated by DNA pulsed field gel electrophoresis [5,6]. One of the characteristic features of this minichromosome, which we observed earlier [6], is that introduction of one DSB causes a change of chromatin structure that prevents induction of further DSBs in the same molecule.…”

Section: Experimental Model and Initial Mathematical Modelingmentioning

confidence: 78%

Modeling the repair of DNA strand breaks caused by γ-radiation in a minichromosome

et al. 2014

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The objective of the studies described here was the development of a mathematical model which would fit experimental data for the repair of single and double strand breaks induced in DNA in living cells by exposure to ionizing radiation, and which would allow to better understand the processes of DNA repair. DNA breaks are believed to play the major role in radiation-induced lethality and formation of chromosome deletions, and are therefore crucial to the response of cells to radiotherapy. In an initial model which we reported on the basis of data for the repair of Epstein-Barr minichromosomes in irradiated Raji cells, we assumed that DNA breaks are induced only at the moment of irradiation and are later removed by repair systems. This work gives a development of that mathematical model which fits the experimental results more precisely and suggests strongly that DNA breaks are generated not only by direct irradiation but also later, probably by systems engaged in repair of oxidative damage.

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Section: Experimental Model and Initial Mathematical Modelingmentioning

confidence: 78%

Modeling the repair of DNA strand breaks caused by γ-radiation in a minichromosome

et al. 2014

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“…It has also an impact on the genetic information via poly(ADP-ribose)polymerase-1 that is activated and responsible for DNA strand breaks repair. Caffeine acts as an inhibitor of the enzyme (75).The effect results not only in an alteration in DNA repair,but also in cell cycle control (76,77). The meaning of caffeine ability to inhibit poly(ADP-ribose)polymerase is not fully explored.…”

Section: Interaction Of Caffeine With Receptors and Other Target Strumentioning

confidence: 99%

The perspective of caffeine and caffeine derived compounds in therapy

Pohanka¹

2015

BLL

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Caffeine (1,3,7-trimethylxanthine) is a plant secondary metabolite with a signifi cant impact on multiple processes and regulatory pathways in the body. Though major part of the population meets caffeine via coffee, tea or chocolate, it has also an important role in pharmacology and it is used as a supplementary substance in medicaments. Currently, the ability of caffeine to ameliorate some neurodegenerative disorders is proved in some studies. This review describes basic data about caffeine including toxicity, pharmacokinetics, biological mechanism of the action, and metabolism. Beside this, promising applications of caffeine, new medicaments and derivatives are discussed. Relevant papers and inventions are depicted in the manuscript. Caffeine is a pharmacologically promising substance that deserves big consideration in the current research and development. The compound has several reasons to be an object of scientifi c interest and to be used for pharmacology purposes. Despite an extensive research for a long time, no signifi cantly negative effects on human health were proved hence caffeine can be considered as a completely safe compound. The recent data about amelioration of neurodegenerative and other disorders are promising and deserving more work on the issue. ARTICLE HIGHLIGHTS Caffeine is a purine alkaloid from plants and it has a broad use in current pharmacology. Caffeine is a competitive antagonist of neurotransmitter adenosine on adenosine receptors. The substance is added as a supplementary to drugs and food. Besides interfering on adenosine receptors, caffeine interacts with acetylcholinesterase, monoamine oxidase, phosphodiesterase, ryanodine receptors and others. Current research is devoted to the role of caffeine in neurodegenerative diseases and immunity alteration. New chemical compounds based on caffeine moiety are prepared(Tab. 4, Fig. 6, Ref. 149).

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“…circRNAs and damage repair: DNA breaks are characterized as single- or double strand [ 58 ]. In vivo repair mechanisms support the precise repair of single-strand breaks, while double-strand breaks often lead to cell death[ 59 ].…”

Section: Introduction To Circrnasmentioning

confidence: 99%

Role of circular RNAs in gastrointestinal tumors and drug resistance

Xi¹,

Cai²,

Wang³

et al. 2021

WJCC

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The incidence of gastrointestinal cancers has increased significantly over the past decade and gastrointestinal malignancies now rank among the leading causes of mortality globally. Although newer therapeutic strategies such as targeted therapies have greatly improved patient outcomes, their clinical success is limited by drug resistance, treatment failure and recurrence of metastatic disease. Therefore, there is an urgent need for further research identifying accurate and reliable biomarkers for precise treatment strategies. Circular RNAs (circRNAs) exhibit a covalently closed structure, high stability and biological conservation, and their expression is associated with the occurrence and development of gastrointestinal tumors. Moreover, circRNAs may significantly influence drug resistance of gastrointestinal cancers. In this article, we review the role of circRNAs in the occurrence and development of gastrointestinal cancer, their association with drug resistance, and potential application for early diagnosis, treatment and prognosis in gastrointestinal malignancies. Furthermore, we summarize characteristics of circRNA, including mechanism of formation and biological effects via mRNA sponging, chromatin replication, gene regulation, translational modification, signal transduction, and damage repair. Finally, we discuss whether circRNA-related noninvasive testing may be clinically provided in the future. This review provides new insights for the future development of diagnostics and therapeutics based on circRNAs in gastrointestinal tumors.

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Repair of DNA Strand Breaks in a Minichromosome In Vivo: Kinetics, Modeling, and Effects of Inhibitors

Cited by 8 publications

References 99 publications

Modeling the repair of DNA strand breaks caused by γ-radiation in a minichromosome

Modeling the repair of DNA strand breaks caused by γ-radiation in a minichromosome

The perspective of caffeine and caffeine derived compounds in therapy

Role of circular RNAs in gastrointestinal tumors and drug resistance

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