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Study of the mammalian oncogenic transcription factors in the yeast model
Novák, Josef ; Zámostná, Blanka (advisor) ; Šťovíček, Vratislav (referee)
Yeast serves as a useful tool for studying cellular processes and therefore a large amount of techniques and protocols has been developed. There are special methods for studying the transcriptional factors in yeast, such as modified yeast two-hybrid screens, yeast one-hybrid screens and systems studying ability of transcription factors to transactivate a reporter gene. Oncogenes from AP-1 complex, Myc and Myb protein families are described in this work. Using a yeast model the structural-functional properties of proteins can be easily studied and in some cases even their ability of oncogenic transformation can be predicted (FASAY or ability of c-Myc to transactivate a reporter gene). However, results from yeast models must be confirmed in mammalian cells. 1
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Investigating critical mechanisms of oncogenesis using cell model systems
Hušková, Hana ; Stopka, Tomáš (advisor) ; Macůrek, Libor (referee) ; Vojtěšek, Bořivoj (referee)
(EN) Humans and cells in their bodies are exposed to various mutagens in their lifetime that cause DNA damage and mutations, which affect the biology and physiology of the target cell, and can lead to the expansion of an immortalized cell clone. Genome-wide massively parallel sequencing allows the identification of DNA mutations in the coding sequences (whole exome sequencing, WES), or even the entire genome of a tumour. Mutational signatures of individual mutagenic processes can be extracted from these data, as well as mutations in genes potentially important for cancer development ('cancer drivers', as opposed to 'passengers', which do not confer a comparative growth advantage to a cell clone). Many known mutational signatures do not yet have an attributed cause; and many known mutagens do not have an attributed signature. Similarly, it is estimated that many cancer driver genes remain to be identified. This Thesis proposes a system based on immortalization of mouse embryonic fibroblasts (MEF) upon mutagen treatment for modelling of mutational signatures and identification and testing of cancer driver genes and mutations. The signatures extracted from WES data of 25 immortalized MEF cell lines, which arose upon treatment with a variety of mutagens, showed that the assay recapitulates the...
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Host factors involved in Rous Sarcoma Virus replication
Štafl, Kryštof ; Svoboda, Jan (advisor) ; Horníková, Lenka (referee)
Rous sarcoma virus (RSV) takes a place of honor among retroviruses. Research of RSV allows us to uncover the secret of the origin and evolution of life, the mechanisms of tumorigenesis and the interaction between viruses and their hosts. Viruses are not able to replicate themselves without host cells. They exploit a number of cellular pathways and factors and they can reprogram the cells to produce great amounts of viral progeny. They exert pressure on their host that leads to developement of new types of cellular proteins, which then results in resistance of the cells. This thesis focuses on the host factors involved in the RSV replication cycle. It summarizes the current knowledge about the replication cycle of retroviruses and the host factors that are necessary for productive infection: cellular receptors, endocytic and secretory pathways, nuclear transport, proteosynthesis, replication of proviruses and its stimulation. The restriction mechanisms of cells are also taken into account. The current knowledge about RSV is compared with facts on mammalian retroviruses and gaps in research are highlighted. The influence of the host cell factor absence, host specificity and cellular permissiveness are correlated and discussed.
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Study of the mammalian oncogenic transcription factors in the yeast model
Novák, Josef ; Šťovíček, Vratislav (referee) ; Zámostná, Blanka (advisor)
Yeast serves as a useful tool for studying cellular processes and therefore a large amount of techniques and protocols has been developed. There are special methods for studying the transcriptional factors in yeast, such as modified yeast two-hybrid screens, yeast one-hybrid screens and systems studying ability of transcription factors to transactivate a reporter gene. Oncogenes from AP-1 complex, Myc and Myb protein families are described in this work. Using a yeast model the structural-functional properties of proteins can be easily studied and in some cases even their ability of oncogenic transformation can be predicted (FASAY or ability of c-Myc to transactivate a reporter gene). However, results from yeast models must be confirmed in mammalian cells. 1
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