Chromosomal DNA replication is one of the central biological events occurring 
inside cells. Due to its large size, the replication of genomic DNA in 
eukaryotes initiates at hundreds to tens of thousands of sites called DNA 
origins so that the replication could be completed in a limited time. Further, 
eukaryotic DNA replication is sophisticatedly regulated, and this regulation 
guarantees that each origin fires once per S phase and each segment of DNA gets 
duplication also once per cell cycle. The first step of replication initiation 
is the assembly of pre-replication complex (pre-RC). Since 1973, four proteins, 
Cdc6/Cdc18, MCM, ORC and Cdt1, have been extensively studied and proved to be 
pre-RC components. Recently, a novel pre-RC component called Sap1/Girdin was 
identified. Sap1/Girdin is required for loading Cdc18/Cdc6 to origins for pre-RC 
assembly in the fission yeast and human cells, respectively. At the transition 
of G1 to S phase, pre-RC is activated by the two kinases, cyclindependent kinase 
(CDK) and Dbf4-dependent kinase (DDK), and subsequently, RPA, primase-polα, 
PCNA, topoisomerase, Cdc45, polδ, and polɛ are recruited to DNA origins for 
creating two bi-directional replication forks and initiating DNA replication. As 
replication forks move along chromatin DNA, they frequently stall due to the 
presence of a great number of replication barriers on chromatin DNA, such as 
secondary DNA structures, protein/DNA complexes, DNA lesions, gene 
transcription. Stalled forks must require checkpoint regulation for their 
stabilization. Otherwise, stalled forks will collapse, which results in 
incomplete DNA replication and genomic instability. This short review gives a 
concise introduction regarding the current understanding of replication 
initiation and replication fork stabilization.