Eukaryotic DNA replication: Orchestrated action of multi-subunit protein complexes

Mutation Research
Sukhyun KangKyungjae Myung

Abstract

Genome duplication is an essential process to preserve genetic information between generations. The eukaryotic cell cycle is composed of functionally distinct phases: G1, S, G2, and M. One of the key replicative proteins that participate at every stage of DNA replication is the Mcm2-7 complex, a replicative helicase. In the G1 phase, inactive Mcm2-7 complexes are loaded on the replication origins by replication-initiator proteins, ORC and Cdc6. Two kinases, S-CDK and DDK, convert the inactive origin-loaded Mcm2-7 complex to an active helicase, the CMG complex in the S phase. The activated CMG complex begins DNA unwinding and recruits enzymes essential for DNA synthesis to assemble a replisome at the replication fork. After completion of DNA synthesis, the inactive CMG complex on the replicated DNA is removed from chromatin to terminate DNA replication. In this review, we will discuss the structure, function, and regulation of the molecular machines involved in each step of DNA replication.

Citations

Jan 22, 2019·European Journal of Human Genetics : EJHG·Mark E Samuels, Philippe M Campeau
Jun 5, 2019·Nature Communications·Mi-Sun KangKyungjae Myung
Jul 3, 2020·Nature Reviews. Molecular Cell Biology·Matteo BertiMassimo Lopes
Feb 3, 2018·International Journal of Molecular Medicine·Longxiang TuDewu Liu
Aug 28, 2020·Journal of Virology·Bo Liang
Dec 17, 2020·International Journal of Molecular Sciences·Milena Denkiewicz-KrukIwona J Fijalkowska

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