Mechanisms of Chromosomal DNA Replication Initiation and Stabilization of Replication Forks in Eukaryotes

Abstract

In eukaryotes, DNA replication initiates at multiple and specific sites on chromosomal DNA. When cells are in late M and G1 phases, Cdc6/Cdc18, Cdt1 and MCM are loaded to ORC binding sites on DNA replication origins to form pre-RC (pre-replication complex). Pre-RC is activated at the transition of G1 to S phase. Subsequently, those proteins that act at replication forks bind to DNA origins to form two bidirectional replication forks for initiating DNA synthesis. On chromosome, the moving replication forks often encounter replication fork barriers (DNA secondary structure, some protein binding sites, damaged bases) and stall. The stalled forks require checkpoint control to maintain fork stability; otherwise, stalled forks will collapse and genomic integrity is compromised. This article gives a brief review about current understanding of the mechanism of replication initiation and replication fork stabilization.