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Formation of complex chromosomal rearrangements in cancer cells and significance of these events
Rochlová, Kristina ; Zemanová, Zuzana (advisor) ; Rothová, Olga (referee)
Chromoanagenesis is a catch-all term of recently described catastrophic events that generate complex karyotypes. These events are divided according to the characteristic features and are termed chromothripsis, chromoplexis and chromoanasynthesis. Chromothripsis represents a disintegration of chromosomes or their parts into hundreds of small fragments. Those chromosome fragments are then incorrectly reassembled. Chromoplexis rearrangements are not very different from chromothripsis rearrangements. The main difference is a lower number of breakpoints and the distribution of aberrations in the whole genome. The erroneous replication processes occur during chromoanasynthesis. There are several mechanisms responsible for breakdowns of a DNA molecule. In the case of chromothripsis, micronucleus formation is probably the most important mechanism. During chromoplexis, transcriptional stress plays a major role. Replication stress is associated with chromoanasynthesis rearrangements. The result of all these processes are highly rearranged chromosomes with numerous losses or gains of genetic material. This work summarizes the current knowledge of the mechanisms that are mentioned above and the genesis of complex aberrations. At the same time, it represents the connection between complex karyotype and clonal...
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Aktivita telomerázy u termita \kur{Prorhinotermes simplex}
JEHLÍK, Tomáš
Social insect is known for its unique caste system, coherence and effective division of labor, but also for the extreme longevity of reproductive individuals in comparison with asexual castes. Although mechanisms leading to lifespan differences between reproductive and non-reproductive castes of social insects are not sufficiently explained, one of the longevity determinants might be telomere length and activity of telomerase as the most common mechanism of telomere length maintenance. Telomere length belongs to general indicators of organismal lifespan. This work is focused on monitoring of telomerase activity in various stages, castes and organs of the termite Prorhinotermes simplex (Isoptera: Rhinotermitidae) showing up-regulation of telomerase in reproductive castes.
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Alternativní telomerické kompenzační mechanismy jako způsob adaptace telomer vůči stresovým podmínkám v průběhu evoluce hmyzu
KRŮČEK, Tomáš
Telomeres are special nucleoprotein structures at the ends of eukaryotic chromosomes. Because of incomplete DNA replication telomere length becomes shorter with each cell cycle. Several mechanisms of telomere maintenance have been identified. Although the most common mechanism is the activity of telomerase that synthesizes short telomeric sequences onto chromosome ends, telomere length might be elongated by alternative ways such as the retrotransposition of special telomeric mobile elements targeted to chromosome ends, found in Drosophila, and homologous recombination. Homologous recombination extends satelite sequences in some dipteran species and also serves in vertebrates as the alternative mechanism to telomerase. The (TTAGG)n sequence was designated as the insect telomeric sequence. Although the (TTAGG)n sequence was found at telomeres of most of the tested insect orders in previous studies, there are numerous insect species showing the (TTAGG)n absence. Diptera is the large insect order, which shows the lost of the (TTAGG)n sequence together with telomerase system and its replacement by the transposition of telomeric elements in Drosophila or homologous recombination in mosquitoes or midges. The (TTAGG)n sequence was reported as telomeric sequence in most insect orders, however, the (TTAGG) specific telomerase activity was not tested in these orders.Therefore, I first speculated that non-telomerase systems in insects may not be limited only to Diptera and the presence of non-telomerase systems in insect might be underestimated. When I tested a distribution of the TTAGG-specific telomerase activity I confirmed that the telomerase system is the most comon telomere length compensation mechanism in insect, however, it is not present in Zygentoma, Orthoptera and Phasmida, which are insect orders with a previously reported presence of the (TTAGG)n telomeric motif. Data of the thesis showed that the activity of telomeric retrolements at Drosophila is up-regulated by mild-levels of free radical species, enhancing telomere extension. The role of non-telomerase mechanisms to overcome stress conditions during evolution of insect telomeres is hypothesized.
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Molecular composition of constitutive heterochromatin
Pajpach, Filip ; Král, Jiří (advisor) ; Holá, Dana (referee)
Constitutive heterochromatin of eukaryotes includes various types of repetitive DNA and transposons characteristic for given region. DNA of centromeric and telomeric re- gions is usually highly methylated and transcribed to RNA transcripts, which participate in formation, functions and spreading of heterochromatin along with histones, their mod- ifications and non-histone proteins. The most typical histone modification in heterochro- matin is methylation, which forms the binding site for protein HP1. This protein (and his paralogues in other eukaryotes except for S. cerevisiae) participates in formation of com- plexes including other proteins like histone methylases SUV39H and their paralogues. Es- sential are also telosome proteins regulating telomeric heterochromatin, Polycomb group proteins and many others, for instance MBD1, Epe1, SUMO and DNA methylases DNMT. Many proteins form complexes, which partake in mechanisms necessary for heterochro- matin maintenance, for example RDRC and RITS complexes in RNA interference, SHREC complex in heterochromatin spreading, and PRC complexes forming heterochromatin in specific situations. Key words: centromere, DNA, histone, HP1, constitutive heterochromatin, methylation, modification, protein, RNA, specific, telomere
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Yeast gene silencing.
Tarabová, Eva ; Kuthan, Martin (advisor) ; Schierová, Michaela (referee)
Each cell contains a complete copy of the entire genetic equipment of the organism. However not all genes are expresed, cells are differentiated in higher eukaryots and only certain proteins are transcribed in each cell. This is possible thanks to a gene silencing, that is stable throughout the whole cell cycle and epigeneticaly inherited from one generation to another. Gene silencing serves also in the maintainance of the chromosomal integrity, it is connected with the right progression of the cell division. It even enables mating type switching and ensures right cells' identity in yeasts. The basis is compact and a higher-ordered structure of chromatin called heterochromatin. The mechanism is common to many various organisms, although the proteins, which ensure silencing, are different.
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