Function and organization of G-quadruplexes in the genome

Nukleinske kiseline mogu poprimiti različite oblike sekundarne strukture. Jedna od takvih struktura nastaje u sljedovima bogatim dušičnom bazom gvanin, pri čemu se četiri gvanina vodikovim vezama povezuju u planarnu strukturu G-kvarteta. Nekoliko G-kvarteta naslaganih jedan na drugi i poduprijeti šećerno-fosfatnom okosnicom tvore sekundarnu strukturu G-kvadripleksa. G-kvadripleksi mogu nastati kao dio deoksiribonukleinskih kiselina i kao dio ribonukleinskih kiselina. Važan su dio genoma eukariota, prokariota i virusa. U eukariotskim genomima pronalaze se u telomerama, promotorima gena te u transkriptomu. Njihova funkcija određena je položajem u genomu. Važni su regulatori aktivnosti telomeraze, transkripcije gena i translacije proteina, ali i poliadenilacije i prekrajanja introna. Mogu se detektirati in vivo pomoću antitijela i imunofluorescencijom, a dijelovi genoma s potencijalom formiranja G-kvadripleksa određuju se računalnim algoritmima. Male molekule ili ligandi mogu se specifično vezivati i stabilizirati sekundarnu strukturu G-kvadripleksa. Stabilizacijom G-kvadripleksa u pojedinim regijama genoma moguće je potisnuti proliferaciju tumora, zbog čega se ovakvi ligandi intenzivno istražuju s ciljem pronalaska antitumorskih lijekova.Nucleic acids can adopt various types of secondary structures. One of such structures arises in guanine-rich sequences, where four guanines link with hydrogen bonds in the planar G-quartet structure. Few G-quartets stacked on each other and supported by the sugar-phosphate backbone create a G-quadruplex secondary structure. G-quadruplexes can arise as a part of the deoxyribonucleic acids, as well as ribonucleic acids. They are an important part of the eukaryote, prokaryote, and virus genomes. In eukaryotic genomes, they can be found in telomeres, gene promoters, and as part of the transcriptomes. Their function is determined by their position in the genome. They are important regulators of telomerase activity, gene transcription, protein translation, polyadenylation, and intron splicing. In vivo detection of G-quadruplexes is possible using antibodies and immunofluorescence, and part of the genome with the potential of forming G-quadruplex can be determined using computational algorithms. Small molecules or ligands can specifically bind and stabilize the secondary structure of Gquadruplexes. By stabilizing the G-quadruplex structures in certain regions of the genome, it is possible to suppress the proliferation of tumors, which is why such ligands are intensively researched with the aim of finding antitumor therapeutics