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Critical Analysis of Housing and Prediction of its Development Prediction
Leitnerová, Aneta ; Fajkus, Jiří (referee) ; Škapa, Stanislav (advisor)
The diploma thesis "Critical analysis of the housing stock and prediction of its devel-opment" provides comprehensive information of the residential market development in the context of demographic, political and economic factors. This thesis explores the possibility of involvement of methodological ways to improve market transparency in the housing and its development and research. Analysis of residential market contained in the first few chapters is based on predicting the market in terms of optimistic, pessimistic and realistic market devel-opment assuming the interaction of certain macroeconomic and microeconomic conditions according to the scenario.
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Molecular mechanisms of Wip1 phosphatase function in DNA damage response
Štorchová, Radka ; Macůrek, Libor (advisor) ; Fajkus, Jiří (referee) ; Líčeníková Hořejší, Zuzana (referee)
Human cells are constantly exposed to diverse factors causing DNA lesions, which activate the DNA damage response (DDR). Depending on the severity of DNA damage, DDR can promote temporary cell cycle arrest (checkpoint), permanent growth arrest (senescence) or programmed cell death (apoptosis). DDR signalling is regulated by a cascade of post- translational modifications, where key mediators are represented by protein kinases ATM, ATR and DNA-PK. Wip1 phosphatase (encoded by PPM1D gene) plays an important role in DDR termination by dephosphorylation of many targets of these kinases. In this thesis, we investigated checkpoint-independent functions of PPM1D in cells and described several new substrates. We discovered, that PPM1D interacts with the shelterin complex and localizes at telomeres. PPM1D dephosphorylates the shelterin component TRF2 at S410. TRF2 S410 phosphorylation enhanced TRF2 interaction with TIN2, indirectly also increasing recruitment of TPP1 to telomeres. Importantly, cells over expressing PPM1D showed increased number of telomeric fusions. These findings might be very relevant for some cancer types, in particular those expressing high levels of PPM1D or carrying C-terminally truncated mutations in PPM1D. To validate the published substrates and to detect possible new targets of...
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Mechanisms of DNA repair in the moss Physcomitrella patens
Holá, Marcela ; Angelis, Karel (advisor) ; Bříza, Jindřich (referee) ; Fajkus, Jiří (referee)
Over the course of an organism's life, its genome is exposed to endogenous and exogenous chemical, physical and biological agents - genotoxins. These genotoxins alter its basic structural components - sugar residues, phosphodiester bonds, and nitrogenous bases. Organisms have therefore evolved a plethora of different strategies to both repair DNA lesions and maintain genomic stability. These DNA repair pathways are linked with several other cell pathways, including chromatin remodelling, DNA replication, transcription, cell cycle control, apoptosis - programmed cell death (PCD), thereby providing a coordinated cellular response to DNA damage. Biochemical mechanisms of DNA repair are relatively well understood in yeast and mammals, however, far less so in plants. While these repair mechanisms are evolutionary conserved, significant differences still remain. Therefore, further investigation is required. This thesis summarises the introduction of a novel plant model - the moss, Physcomitrella patens (Physcomitrella). As a haploid gametophyte with unique characteristics of high frequency of homologous recombination (HR), and apical growth of filaments, it is an ideal organism to study DNA repair in plants. Previous research on Physcomitrella regarding mechanisms of DNA lesion repair induced by...
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Modulation of human telomerase activity by nucleoside and nucleotide analogues
Hájek, Miroslav ; Votruba, Ivan (advisor) ; Fajkus, Jiří (referee) ; Hejnar, Jiří (referee)
CONCLUSIONS Considering human telomerase as a promising target of anti-cancer therapy, the thesis deals with the study of inhibitory potency of selected ANP diphosphates towards telomerase, and the capability of nucleoside-type DNA methylation inhibitors to inhibit hTERT expression, knowing that hTERT expression closely correlates with telomerase activity in vitro and in vivo. The results can be summarized as follows: All the purine ANP diphosphates except for (S)-PMPApp and 6-Me2PMEDAPpp show dose- dependent inhibition of human telomerase in cell-free assay, the adenine derivatives are less effective inhibitors than the guanine derivatives. The only two pyrimidine ANP diphosphates tested (PMECpp and PMETpp) do not show any significant inhibitory potency towards telomerase. Activity of tested ANPs on telomerase is limited to their diphosphates (ANPpp) only. (R)-enantiomers are more inhibitory compared to (S)-enantiomers. This indicates that absolute configuration plays an important role in the telomerase inhibition and that the enzyme distinguishes between the (R)- and (S)-enantiomers. PMEGpp is the most potent human telomerase inhibitor among all ANPs studied with the IC50 value of 12.7 ± 0.5 mol.l-1 at 125 M dNTPs. Its inhibitory potency towards telomerase is comparable to that of ddGTP (IC50...
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Dynamics of de novo DNA methylation and its impact on transgene expression and CRISPR/Cas9 mutagenesis
Přibylová, Adéla ; Fischer, Lukáš (advisor) ; Pečinka, Aleš (referee) ; Fajkus, Jiří (referee)
Genetic information must be protected, maintained and copied from cell to daughter cells, from generation to generation. In plants, most of the cells contain complete genetic information, and many of these cells can regenerate to a whole new plant. Such a feature leads to the need for precise control of which genes will be active and which not because in growth and differentiation, only the activity of specific genes for the individual cells, tissues, organs are required. One of the mechanisms controlling the gene activity is RNA interference (RNAi), which down- regulates or blocks the expression of specific genes at the transcriptional or post-transcriptional level. The crucial part of the RNAi is guiding the RNAi machinery to the target. It is mediated via sequence complementarity of the target with a small RNA (sRNA), which is diced from a double- stranded RNA (dsRNA) precursor. The molecular mechanism of dsRNA and sRNA formation and also the target origin predestinates the subsequent silencing pathway. In transcriptional gene silencing (TGS), the gene expression is regulated through chromatin epigenetic modifications. One of the epigenetic marks is cytosine methylation, which is established mainly by RNA-directed DNA-methylation (RdDM) pathway. Although the protein machinery was relatively...
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Modulation of human telomerase activity by nucleoside and nucleotide analogues
Hájek, Miroslav ; Votruba, Ivan (advisor) ; Fajkus, Jiří (referee) ; Hejnar, Jiří (referee)
CONCLUSIONS Considering human telomerase as a promising target of anti-cancer therapy, the thesis deals with the study of inhibitory potency of selected ANP diphosphates towards telomerase, and the capability of nucleoside-type DNA methylation inhibitors to inhibit hTERT expression, knowing that hTERT expression closely correlates with telomerase activity in vitro and in vivo. The results can be summarized as follows: All the purine ANP diphosphates except for (S)-PMPApp and 6-Me2PMEDAPpp show dose- dependent inhibition of human telomerase in cell-free assay, the adenine derivatives are less effective inhibitors than the guanine derivatives. The only two pyrimidine ANP diphosphates tested (PMECpp and PMETpp) do not show any significant inhibitory potency towards telomerase. Activity of tested ANPs on telomerase is limited to their diphosphates (ANPpp) only. (R)-enantiomers are more inhibitory compared to (S)-enantiomers. This indicates that absolute configuration plays an important role in the telomerase inhibition and that the enzyme distinguishes between the (R)- and (S)-enantiomers. PMEGpp is the most potent human telomerase inhibitor among all ANPs studied with the IC50 value of 12.7 ± 0.5 mol.l-1 at 125 M dNTPs. Its inhibitory potency towards telomerase is comparable to that of ddGTP (IC50...
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Mechanisms of DNA repair in the moss Physcomitrella patens
Holá, Marcela ; Angelis, Karel (advisor) ; Bříza, Jindřich (referee) ; Fajkus, Jiří (referee)
Over the course of an organism's life, its genome is exposed to endogenous and exogenous chemical, physical and biological agents - genotoxins. These genotoxins alter its basic structural components - sugar residues, phosphodiester bonds, and nitrogenous bases. Organisms have therefore evolved a plethora of different strategies to both repair DNA lesions and maintain genomic stability. These DNA repair pathways are linked with several other cell pathways, including chromatin remodelling, DNA replication, transcription, cell cycle control, apoptosis - programmed cell death (PCD), thereby providing a coordinated cellular response to DNA damage. Biochemical mechanisms of DNA repair are relatively well understood in yeast and mammals, however, far less so in plants. While these repair mechanisms are evolutionary conserved, significant differences still remain. Therefore, further investigation is required. This thesis summarises the introduction of a novel plant model - the moss, Physcomitrella patens (Physcomitrella). As a haploid gametophyte with unique characteristics of high frequency of homologous recombination (HR), and apical growth of filaments, it is an ideal organism to study DNA repair in plants. Previous research on Physcomitrella regarding mechanisms of DNA lesion repair induced by...
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Identification and characterization of transcription facotrs affecting late stages of male gametophyte development in Arabidopsis thaliana
Dupľáková, Nikoleta ; Honys, David (advisor) ; Bříza, Jindřich (referee) ; Fajkus, Jiří (referee)
Conclusions My thesis was devoted to the investigation of a complex regulatory network of transcription factors in the Arabidopsis thaliana male gametophyte. In addition to the abovementioned objective, the second aim of the thesis was the creation of a web-based transcriptome database and data mining tool characterized by an innovative concept of presentation and evaluation of the data from DNA chips. The results of my thesis can be summarized as follows: 1. We created a database called Arabidopsis Gene Family Profiler (arabidopsisGFP) (http://agfp.ueb.cas.cz/) which was made available on-line. This database was developed in order to provide a new tool for presentation of gene expression data (transcriptome), allowing the user to display the data in a quick and intuitive way using the innovative and when launched also unique concept of a virtual plant. The database employs a progressive idea "from simple to complex", but also provides the user with more traditional data presenting options. The aGFP database can serve as a reference manual for the expression of individual genes and gene families in Arabidopsis thaliana under physiological conditions at different phases of the life cycle and in individual organs and tissues or cell types. 2. A chapter reviewing available servers for deposition of the...
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