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The main topic of the text is the structure and function of minichromosome maintenance (Mcm) proteins in DNA replication. Mcm proteins form the Mcm2-7 double hexamer, crucial for replication fork formation and DNA unwinding. The text discusses the helicase activity of Mcm proteins, their ATPase function, and the regulation of their localization during the cell cycle. It also covers the formation of the pre-replication complex and the critical roles of Cdc45 and GINS in replisome progression.
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Mcm proteins assemble into a complex known as the Mcm2-7 double hexamer, which is essential for the formation of the replication fork
Each Mcm protein has conserved sequences indicating distinct functions necessary for DNA replication
Mcm proteins play a vital role in the helicase activity of the Mcm complex, which is responsible for unwinding the DNA during replication
The intracellular localization of Mcm proteins is carefully regulated throughout the cell cycle to ensure proper DNA replication
Mcm proteins are predominantly nuclear during the G1 and S phases, but are exported to the cytoplasm during the G2 and M phases
CDKs promote the nuclear export of Mcm proteins, but those bound to chromatin are protected due to their involvement in replication
The pre-RC is formed during the G1 phase through the binding of replication initiation factors to replication origins
The pre-RC is activated by S phase-specific kinases, CDK and Dbf4-dependent kinase (DDK), which phosphorylate the Mcm4 subunit
CDK and DDK facilitate the recruitment of Cdc45 and GINS to the Mcm complex, marking the formation of the active CMG helicase and the start of DNA synthesis
Cdc45 is essential for both the initiation and elongation phases of DNA replication and is recruited to replication origins
The GINS complex is crucial for the interaction between Mcm and Cdc45 at replication origins and replication forks
Cdc45, Mcm2-7, and GINS together form the CMG helicase, which is responsible for the efficient unwinding of DNA during replication
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Function of Mcm proteins in DNA replication initiation and elongation
Mcm proteins are crucial for starting DNA replication and aiding the replication fork's progression in eukaryotic cells.
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Configuration of Mcm2-7 double hexamer on DNA
The Mcm2-7 double hexamer forms a head-to-head arrangement on DNA, creating a central channel for DNA and a kink for stability.
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Role of CMG helicase in DNA replication
The CMG helicase, composed of Cdc45-MCM-GINS, is the catalytic core that unwinds the DNA helix during replication.
