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DNA replication licensing factor MCM4

Definition:

Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.

References:

[1]. Yasemin Baris, et al. Fast and efficient DNA replication with purified human proteins. Nature. 2022 Jun;606(7912):204-210. [Content Brief]

[2]. Y Ishimi, et al. A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. J Biol Chem. 1997 Sep 26;272(39):24508-13. [Content Brief]

[3]. Michael Jenkyn-Bedford, et al. A conserved mechanism for regulating replisome disassembly in eukaryotes. Nature. 2021 Dec;600(7890):743-747. [Content Brief]

[4]. Neil J Rzechorzek, et al. CryoEM structures of human CMG-ATPγS-DNA and CMG-AND-1 complexes. Nucleic Acids Res. 2020 Jul 9;48(12):6980-6995. [Content Brief]

[5]. Morgan L Jones, et al. Structure of a human replisome shows the organisation and interactions of a DNA replication machine. EMBO J. 2021 Dec 1;40(23):e108819. [Content Brief]

[6]. Yukio Ishimi, et al. G364R mutation of MCM4 detected in human skin cancer cells affects DNA helicase activity of MCM4/6/7 complex. J Biochem. 2015 Jun;157(6):561-9. [Content Brief]

[7]. Toshiya Tsuji, et al. Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells. Mol Biol Cell. 2006 Oct;17(10):4459-72. [Content Brief]

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