Identifikace a characterizace kvadruplex formujících segmentů v promotorové DNA.

In this thesis we study posibilities of selective targetting of aberrant FGFR3 signaling by using DNA G-quadruplexes (G4) localised in promoter region of fgf2, fgf3, fgfr2 a fgfr3 genes. In this work we describe biological function of these genes and their role in aberrant FGFR3 signaling causing skeletal dysplasias, than this work focus on the role of G4´s in regulation of gene expression. This work suggest the way of selective targetting of FGFR3 signaling by genome inspired G4 aptamers. To acheve this goal we run the bioinformatics analysis of promoter regions of studied genes and according to this analysis we designed G4 oligonucleotides. We run phenotype assay on RCS chondrocytes to verify the ability to interact with FGFR3 signaling of these oligonucleotides . Secondary structure of oligonucleotides was verified by NMR spectroscopy and related to results of bioinformatics analyse and phenotype assay. This work is also focused on study the possibilities for regulation fgf2, fgf3, fgfr2 and fgfr3 genes expresion by interactong with G4´s in promter region of these genes and we desribe the preparation of plasmid reporter system for studiing the role of G4´s localised i promoter region of fgf2, fgf3, fgfr2 and fgfr3 genes in regulation of their gene expression. Results of this work can propose the strategy for effective targeting of FGFR3 signaling.