Spatiotemporal control of DNA replication in Saccharomyces cerevisiae

Abstract:

DNA replication is one of the fundamental processes of all lives. Errors produced by DNA replication and abnormalities in its regulation are major sources of genomic instability in cells, leading to abnormal cell growth, aging, tumorigenesis and even death. In order to ensure accurate and complete duplication of genomic DNA, DNA replication is strictly regulated in all eukaryotes. In the G1 phase, the core component of the DNA replicative helicase——Mcm2-7 is recruited to the origins. This is called replication licensing. After cells entering the S phase, the helicase co-activators Cdc45 and GINS are recruited to Mcm2-7, forming the helicase holoenzyme Cdc45-Mcm2-7-GINS (CMG) complex. Subsequently, numerous replicating proteins are recruited to the CMG platform under precise spatiotemporal control and assembled into a replication machine to initiate bidirectional replication. When two converging replication forks encounter each other, CMGs are displaced to terminate the progression of these forks. The last decade has witnessed the leap-forward breakthroughs in this field, particularly in the model organism Saccharomyces cerevisiae. Here, we summarize the recent advances in eukaryotic DNA replication with a focus on the motor of replisome, DNA helicase CMG.