DNA replication and maintenance of genome stability

U radu je najprije prikazan mehanizam replikacije DNA eukariotskih stanica. Sinteza molekule DNA bazirana je na specifičnom Watson-Crick sparivanju baza koje predstavljaju jedan od najvažnijih motiva u sekundarnoj strukturi DNA. Termodinamika stvaranja parova baza opisana je modelom najbližih susjeda (engl. nearest neigbor model). Kromosomi eukariotskih stanica su linearni i dugački pa su time često podložni stvaranju različitih neuobičajenih struktura koje ometaju replikacijske rašlje ali često i olakšavaju procese u koje je uključena molekula DNA. Zbog toga su opisane osnove topologije i najčešće alternativne strukture DNA strukture. Zadaci koji se moraju izvršiti tijekom replikacije zahtijevaju međusobnu koordinaciju i stoga nije iznenađujuće da defekti u replikaciji DNA uzrokuju brojne ljudske bolesti. Iz tog razloga opisana je kontrola staničnog ciklusa i mehanizmi koji omogućavaju zaobilaženje mjesta oštećenja.This thesis first presents the mechanism of replication of eukaryotic cells. DNA synthesis is based on specific Watson-Crick base pairing, which provide a simple structural code of DNA secondary structure formation. Nearest-neighbor model predict the thermodynamic parameters for for Watson-Crick base pairs. Long linear eukaryotic chromosomes are often susceptible to creating unusual DNA structures that can cause stalling of replication fork but often they can facilitate certain DNA processes. Therefore, the principles of DNA topology and the most common alternative DNA structures are described. Many complex tasks that must be performed during DNA replication require co-ordination and accordingly it is not surprising that defects in DNA replication cause many human diseases. For this reason, the cell cycle control mechanisms and damage tolerance pathways are described as following