Kırmacı, Fahriye Nur
DNA has multiple levels of regulations owing to complex regulatory units. Promoters are among the most crucial regulatory sequence units in DNA, altering transcription initiation. Recent studies have shown that secondary structures called G-quadruplexes (G4s) can be found in promoter regions of certain genes along with the common double-helical Watson-Crick DNA. G-quadruplexes are four-stranded helical structures formed by the π-π stacking of G-tetrad structures with a pattern called G-tracts. New findings suggest that these noncanonical structures are transcriptionally altering the expression of critical proteins in healthy cells and possibly involved in the formation of cancerous tissue. For this reason, the promoter regions that have the capacity to form G-quadruplex structures have become the target of many drug development efforts against cancer. Within the scope of this thesis, it is revealed that five Azacyanine derivatives (Azamethyl, Aza4, Aza5, Azabutyl, and Azaisobutyl) were preferentially binding to the c-MYC (Cellular Myelocytomatosis) promoter region over the G4 forming promoter regions of B-Cell CLL/lymphoma 2 (BCL-2), Vascular Endothelial Growth Factor (VEGF), Kirsten Rat Sarcoma (KRAS), Human Epidermal Growth Factor Receptor 2 (HER-2) and Retinoblastoma (RB) via competition dialysis. Interactions of G4 c-MYC and Azamethyl were investigated further using UV-Vis, Fluorescence, and Circular Dichroism spectroscopy. G4 of c-MYC promoter region was found to be stabilized by Azamethyl via thermal denaturation studies. Thermal denaturation temperature of c-MYC was shifted up to 20°C with varying Azamethyl concentration. Lastly, fluorescence spectroscopy unveiled the association constant between c-MYC and Azamethyl as 2.9 x 105 ±1.4 x 104 M-1.


Expression and activity analyses of industrially important extracellular enzymes produced by a bacilysin knock-out mutant of Bacillus Subtilis
Aytekin, Samet; Özcengiz, Gülay; Okay, Sezer; Department of Molecular Biology and Genetics (2018)
Bacilysin, the smallest peptide antibiotic known to date, is produced non-ribosomally by Bacillus subtilis by the collective actions of seven proteins transcribed from bacABCDEF operon and bacG gene. Bacilysin is a two-amino acid peptide composed of L-alanine and a modified amino acid, L-anticapsin. Bacilysin biosynthesis was shown to be strongly regulated by quorum sensing through the actions of global regulator proteins including Spo0K, Spo0H, Spo0A, ComQ/ComX, ComP/ComA as well as several Phr proteins, O...
Association between XRCC3 Thr241Met polymorphism and laryngeal cancer susceptibility in Turkish population
Mutlu, Pelin; Yalcin, Serap; Yaylaci, Atilay; Unsoy, Gozde; Saylam, Guleser; Akm, Istemihan; Gündüz, Ufuk (2015-12-01)
DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair genes such as X-ray repair cross-complementing group 3 (XRCC3), can cause a change in protein activity which results in cancer susceptibility. The aim of this study was to investigate the association of XRCC3 Thr241Met single nucleotide polymorphism (SNP), smoking and alcohol consumption with the risk of laryngeal cancer in Turkish population. The frequencies of Thr241Met SNP were studied in 58 laryngeal cancer ...
Induction and control of large-scale gene regulatory networks
Tan, Mehmet; Tan, Mehmet; Department of Computer Engineering (2009)
Gene regulatory networks model the interactions within the cell and thus it is essential to understand their structure and to develop some control mechanisms that could effectively deal with them. This dissertation tackles these two aspects. To handle the first problem, a new constraint-based modeling algorithm is proposed that can both increase the quality of the output and decrease the computational requirements for learning the structure of gene regulatory networks by integrating multiple biological data...
Impact of UV treatment for the removal of bacterial genes during wastewater treatment
Bulut, Taliye; İçgen, Bülent (null; 2018-06-23)
Wastewater treatment plants (WWTPs) are considered as important hotspots for the spread of the antibiotic resistance genes (ARGs). The dissemination of ARGs is one of the most significant threat to public health. This also causes a danger for water quality in surface waters and groundwater. These waters can easily be included in human life by their use in places such as agriculture, livestock and drinking waters. The bacterial gene is important to analyze the quantity of the total bacterial load and to norm...
Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex
Zhang, Heng; Devoucoux, Maëva; Song, Xiaosheng; Li, Li; Ayaz, Gamze; Cheng, Harry; Tempel, Wolfram; Dong, Cheng; Loppnau, Peter; Côté, Jacques; Min, Jinrong (Elsevier BV, 2020-3)
MBTD1, a H4K20me reader, has recently been identified as a component of the NuA4/TIP60 acetyltransferase complex, regulating gene expression and DNA repair. NuA4/TIP60 inhibits 53BP1 binding to chromatin through recognition of the H4K20me mark by MBTD1 and acetylation of H2AK15, blocking the ubiquitination mark required for 53BP1 localization at DNA breaks. The NuA4/TIP60 non-catalytic subunit EPC1 enlists MBTD1 into the complex, but the detailed molecular mechanism remains incompletely explored. Here, we p...
Citation Formats
F. N. Kırmacı, “AFFINITY AND SELECTIVITY OF AZACYANINES TO G-QUADRUPLEX FORMING PROMOTER REGIONS,” M.S. - Master of Science, Middle East Technical University, 2022.