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lüll Initiating DNA synthesis: from recruiting to activating the MCM complex Lei M; Tye BKJ Cell Sci 2001[Apr]; 114 (Pt 8): 1447-54The exact duplication of a genome once per cell division is required of every proliferating cell. To achieve this goal, eukaryotes adopt a strategy that limits every replication origin to a single initiation event within a narrow window of the cell cycle by temporally separating the assembly of the pre-replication complex (pre-RC) from the initiation of DNA synthesis. A key component of the pre-RC is the hexameric MCM complex, which is also the presumed helicase of the growing forks. An elaborate mechanism recruits the MCM complex to replication origins, and a regulatory chain reaction converts the poised, but inactive, MCM complex into an enzymatically active helicase. A growing list of proteins, including Mcm10 and Cdt1, are involved in the recruitment process. Two protein kinases, the Cdc7-Dbf4 kinase (DDK) and the cyclin-dependent kinase (CDK), trigger a chain reaction that results in the phosphorylation of the MCM complex and finally in the initiation of DNA synthesis. A composite picture from recent studies suggests that DDK is recruited to the pre-RC during G1 phase but must wait until S phase to phosphorylate the MCM complex. CDK is required for the recruitment of Cdc45 and other downstream components of the elongation machinery.|*Saccharomyces cerevisiae Proteins[MESH]|Animals[MESH]|Carrier Proteins/metabolism[MESH]|Cell Cycle Proteins/genetics/*metabolism[MESH]|Chromatin/metabolism/ultrastructure[MESH]|Chromosomal Proteins, Non-Histone[MESH]|Cyclin-Dependent Kinases/metabolism[MESH]|DNA Helicases/*metabolism[MESH]|DNA Replication/genetics/*physiology[MESH]|DNA-Binding Proteins/*metabolism[MESH]|DNA/*biosynthesis[MESH]|Humans[MESH]|Minichromosome Maintenance Complex Component 7[MESH]|Minichromosome Maintenance Proteins[MESH]|Nuclear Proteins/metabolism[MESH]|Origin Recognition Complex[MESH]|Saccharomyces cerevisiae/metabolism[MESH] |