Replication initiation and DNA topology: The twisted life of the origin.
Genomic propagation in both prokaryotes and eukaryotes is tightly regulated at the level of initiation, ensuring that the genome is accurately replicated and equally segregated to the daughter cells. Even though replication origins and the proteins that bind onto them (initiator proteins) have diverged throughout the course of evolution, the mechanism of initiation has been conserved, consisting of origin recognition, multi-protein complex assembly, helicase activation and loading of the replicative machinery. Recruitment of the multiprotein initiation complexes onto the replication origins is constrained by the dense packing of the DNA within the nucleus and unusual structures such as knots and supercoils. In this review, we focus on the DNA topological barriers that the multi-protein complexes have to overcome in order to access the replication origins and how the topological state of the origins changes during origin firing. Recent advances in the available methodologies to study DNA topology and their clinical significance are also discussed.
Rampakakis
E
E
Goodman Cancer Centre, Department of Biochemistry, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
Gkogkas
C
C
Di Paola
D
D
Zannis-Hadjopoulos
M
M
D000818:Animals; D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry*; D004261:DNA Replication; D026942:DNA Topoisomerases / Q000378:metabolism; D006801:Humans; D009690:Nucleic Acid Conformation; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D004247:DNA; D026942:DNA Topoisomerases