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Unravelling molecular mechanisms of the abasic crosslink DNA repair
Hušková, Andrea ; Šilhán, Jan (advisor) ; Bařinka, Cyril (referee) ; Pavlíček, Jiří (referee)
4 Abstract DNA as the primary carrier of genetic information guarantees organisms to live, grow, develop and reproduce. However, this most vital molecule in the cell is subject to various damages every moment. If it is not repaired, the cell and the organism will eventually succumb to inevitable destruction. One of the most serious damages is abasic site interstrand crosslink (Ap-ICL). Ap-ICL is formed spontaneously when an abasic site covalently pairs with an adenine on the opposite strand. The lack of information on repair mechanisms, the influence of the local sequence and its stability leads to questions about the fate, toxicity and occurrence of these lesions in cells. During evolution, several mechanisms have evolved to repair these and other damages to ensure the organism's survival. A recently discovered pathway known to repair Ap-ICL is named after the DNA glycosylase responsible for removing Ap-ICL. NEIL3 DNA glycosylase is recruited to Ap-ICL by ubiquitylation of DNA helicase, which is part of the DNA replication complex. NEIL3 glycosylase contains several zinc-finger domains, that bind to the damaged DNA and ensure its catalytic function. The molecular mechanism of the NEIL3 glycosylase repair process is currently not known. In order to answer the aforementioned unknowns, the rate of formation,...
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Self-concept and professional self-concept of adolescents at secondary schools
Hušková, Andrea ; Zvírotský, Michal (advisor) ; Mojžíšová, Jarmila (referee)
The thesis will deal with the relationship of adolescents' self-concept according to their life plans. The work focuses on the issue of their own self-professional concept in their third term of vocational school and fourth term of secondary vocational school. The aim of this work is to describe the relation of the students of the vocational school and secondary vocational school to themselves, how they evaluate themselves, as well as their relation to self-professional concept, to their future goals related to their professional life and further education. The theoretical part deals with their own understanding of self-concept, its development from childhood to adolescence, of the development of themselves and self-professional concept, the importance of life plans for the future life of adolescents on the basis of professional Czech and foreign literature. At the end of the theoretical part, there will be laid theoretical foundations for the research, which will be the content of the practical part of this work. The empirical part of the thesis will analyze the survey made at secondary schools, which focuses on themselves and self-professional concept of selected pupils of the fourth term of secondary vocational schools and the third term of vocational schools. A combination of qualitative and...
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Study of regulation and function of DNA repair enzymes UBE2T and FANCL
Hušková, Andrea ; Šilhán, Jan (advisor) ; Martínková, Markéta (referee)
Due to the action of endogenous and exogenous agents, DNA is subject up to 70,000 lesions per day, thus the existence of repair mechanisms and enzymes is more than necessary. We know basic mechanisms of several specific DNA repair pathways, of which the Fanconi anaemia (FA) repair pathway is one of the least explored. FA is a rare, autosomal recessive disorder characterized by early onset bone marrow failure, developmental defects, genomic instability and predisposition to acute myeloid leukaemia and solid tumours. The primary diagnosis of FA is a hypersensitivity to cross-linking agents of DNA due to inactivation of one of the 21 genes from the FA repair pathway, the so-called FANC genes (FA complementation group). The molecular defect in FA is an impaired repair of DNA interstrand cross-links (ICLs). The ICLs are cytotoxic lesions that inhibit the process of DNA replication and transcription. A crucial step in the FA pathway that initiates ICL repair is a monoubiquitination of FANCD2. FANCD2 monoubiquitination is a base for the recruitment of additional proteins that coordinate DNA repair. Ubiquitin is recruited via activating enzyme E1 (UBA1), ubiquitin-conjugating enzyme E2T (UBE2T) and transferred onto FANCD2 by multisubunit E3 ligase (FA core complex). There are up to 11 different proteins...
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Interaction of gut microflora with myricetin
Hušková, Andrea ; Hodek, Petr (advisor) ; Moserová, Michaela (referee)
Intestinal microflora could be considered a "forgotten" organ of the human body. In the gastrointestinal tract, xenobiotics (including drugs) can be converted into their active or inactive forms by intestinal microorganisms via various metabolic pathways. This, in turn, affects their biological activity. The variability of microorganisms in the hosts intestines leads to diverse metabolic reactions of xenobiotics. Thus, the resulting metabolites may vary across host organisms. It is almost imperative to keep this fact in mind while studying and testing new drugs, as well as dietary supplements, because many microbial metabolites can have serious implications for host organisms, especially when administered orally. In this work, mutual interaction between myricetin and faecal bacteria originating from human intestines was studied under various conditions. For the experiments, a high performance liquid chromatography (HPLC) method was used to determine the rate of myricetin degradation and the potential formation of dihydromyricetin as a reductive metabolite. The effect of myricetin on the growth of faecal bacteria was studied by PCR-DGGE. From the isolated DNA of the bacteria, the DNA sequence corresponding to 16S rRNA was amplified by the PCR method. The PCR products were then separated on a...
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