AFFINITY AND SELECTIVITY OF AZACYANINES TO G-QUADRUPLEX FORMING PROMOTER REGIONS

2022-2-9
Kırmacı, Fahriye Nur
Show full item record
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
120
views
177
downloads
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.
G-Quadruplex, Azacyanine, c-MYC
https://hdl.handle.net/11511/96342
Graduate School of Natural and Applied Sciences, Thesis

Suggestions

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 ...
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...
Essential facilities doctrine under ec competition law and particular implications of the doctrine for telecommunications sectors in Eu and Turkey
Ünver, Mehmet Bilal; Adalı, Orhan; Department of European Studies (2004)
In this study, the origin and main parameters of the Essential Facilities Doctrine are analysed through the case-law that developed out of the application of the EC Competition Rules. Besides putting forward the historical roots, the basic criteria and limitations that apply to the Doctrine are elaborated so as to clarify the legal and analytical foundations of the Doctrine in the EU context. In addition, the added value attributed to the Doctrine in realm of competition policies pursued in network-based in...
The effects of twelve quorum-sensing gene products on the expression of bacabcde operon in bacillus subtilis
Öğülür, İsmail; Özcengiz, Gülay; Department of Biotechnology (2008)
In Bacillus subtilis, genetic competence, sporulation and antibiotic production are controlled by quorum-sensing global regulatory mechanism. Bacilysin, being produced and excreted by certain strains of Bacillus subtilis, is a dipeptide antibiotic composed of L-alanine and L-anticapsin. We showed that the biosynthesis of bacilysin is under the control of quorum sensing global regulatory pathway through the action of ComQ/ComX, PhrC (CSF), ComP/ComA in a Spo0K (Opp)-dependent manner. Recently, the ywfBCDEF g...
Assembly of an antiparallel homo-adenine DNA duplex by small-molecule binding
Persil Çetinkol, Özgül; JAIN, SS; HUD, NV (American Chemical Society (ACS), 2004-07-21)
Molecules that reversibly bind DNA and trigger the formation of non-Watson−Crick secondary structures would be useful in the design of dynamic DNA nanostructures and as potential leads for new therapeutic agents. We demonstrate that coralyne, a small crescent-shaped molecule, promotes the formation of a duplex secondary structure from homo-adenine oligonucleotides. AFM studies reveal that the staggered alignment of homo-adenine oligonucleotides upon coralyne binding produces polymers of micrometers in lengt...
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.
METU IIS - Integrated Information Service open@metu.edu.tr