Replication initiation and DNA topology: The twisted life of the origin
Article first published online: 8 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 110, Issue 1, pages 35–43, 1 May 2010
How to Cite
Rampakakis, E., Gkogkas, C., Di Paola, D. and Zannis-Hadjopoulos, M. (2010), Replication initiation and DNA topology: The twisted life of the origin. J. Cell. Biochem., 110: 35–43. doi: 10.1002/jcb.22557
- Issue published online: 16 APR 2010
- Article first published online: 8 MAR 2010
- Manuscript Accepted: 29 JAN 2010
- Manuscript Received: 27 JAN 2010
- DNA replication;
- replication origins;
- DNA topology;
- chromatin structure
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. J. Cell. Biochem. 110: 35–43, 2010. © 2010 Wiley-Liss, Inc.