Doktorské studium

Studijní obor Biomolekulární chemie

Název práce: Evolutionary conserved structural features of centromeric and telomeric DNA


Předběžné zadání:
Centromeric DNA is evolutionary related to telomeric DNA. Although centromere and telomere virtually differs in almost every aspect of their structure and fundamental function, they share the same evolutionary origin. Recent phylogenetic studies revealed that centromeric DNA evolved from telomeric DNA. The comparative analysis of the centromeric DNA from Drosophila melanogaster, vertebrates and plants showed a common organization: islands of transposons embedded in large regions of simple and/or complex sequence repeats. The sequence analysis of several eukaryotic genomes shows that the (sub)telomeric regions consists of mosaics of repeats and retrotrasposons structured in remarkably similar way. Degenerate telomeric or telomeric-like DNA sequences se are often found in centromeric DNA locus. Comparative analysis among different species suggests that there is no consensus sequence for the centromeric DNA, and even within a single species, it seems that more than one type of DNA may be able to fulfill the centromeric DNA function. In rare cases, when centromeric DNA is lost or damaged, a “new” centromere, called the neocentromere, can form in previously non-centromeric locations of chromosomal DNA including (sub)telomeric regions of chromosomal DNA. Binding of telomere specific proteins to centromeric DNA region in vivo also provides supporting evidence for common evolutionary origin between telomeric and centromeric DNA. A search for “universal centromeric hallmark”: Epigenetically defined centromeric DNA Centromeric DNA has conserved domain structures but no conservation of DNA sequence. It has been demonstrated that whereas coding DNA sequences are organized as a bits and bytes in the computer, the centromeric DNA is organized like a language being defined by characteristics such as rhythm (e.g. alternating purine and pyrimidine sequences) or sequences superstructures (e.g. symmetric sequence motifs). These characteristics were proposed as one of the plausible candidates for “universal centromeric code”. From biophysical point of view, a common property of these “rhythmic” and/or “symmetric” sequence motifs is their specific structural plasticity. In vitro these motifs from centromeric and telomeric DNA can exist, besides B-DNA, in a form of various compact non-B DNA structures such as hairpins, G-quadruplexes, i/motifs, or H-DNA. However, whether the non-B DNA structures are formed under physiological conditions in vivo, and whether they have an active role in (neo)centromere DNA formation and/or its maintenance in the course of cell cycle is unknown. Main aims of the proposed research are threefold. First, the proposed research aims at identification of shared signatures of conformational and topological space of (neo)centromeric and telomeric DNA from several model species. We will pursue two independent evolutionary links: i) signatures of centromeric DNA that are phylogenetically conserved across species, and ii) signatures that evolutionary conserved between centromeric and telomeric DNA within single specie. It is implied that if common structural signatures are to serve as a centromeric hallmark, their formation and stability should be compatible with intra-cellular environment. Second aim of the proposed research is thus a characterization of stability of these signatures under physiological conditions in a complex environment of living cells. As DNA is exposed to variety of nonspecific environmental factors inside a living cell, third aim of the proposed research is the identification of those environmental factors that are actively influencing plasticity of centromeric DNA.
vedoucí:Mgr. Lukáš Trantírek, Ph.D. učo 8725

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