| Structural highlights
Function
MCM2_HUMAN Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. 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. Required for the entry in S phase and for cell division.[1]
Publication Abstract from PubMed
In eukaryotes, DNA replication initiation requires assembly and activation of the minichromosome maintenance (MCM) 2-7 double hexamer (DH) to melt origin DNA strands. However, the mechanism for this initial melting is unknown. Here, we report a 2.59-A cryo-electron microscopy structure of the human MCM-DH (hMCM-DH), also known as the pre-replication complex. In this structure, the hMCM-DH with a constricted central channel untwists and stretches the DNA strands such that almost a half turn of the bound duplex DNA is distorted with 1 base pair completely separated, generating an initial open structure (IOS) at the hexamer junction. Disturbing the IOS inhibits DH formation and replication initiation. Mapping of hMCM-DH footprints indicates that IOSs are distributed across the genome in large clusters aligning well with initiation zones designed for stochastic origin firing. This work unravels an intrinsic mechanism that couples DH formation with initial DNA melting to license replication initiation in human cells.
The human pre-replication complex is an open complex.,Li J, Dong J, Wang W, Yu D, Fan X, Hui YC, Lee CSK, Lam WH, Alary N, Yang Y, Zhang Y, Zhao Q, Chen CL, Tye BK, Dang S, Zhai Y Cell. 2023 Jan 5;186(1):98-111.e21. doi: 10.1016/j.cell.2022.12.008. PMID:36608662[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Todorov IT, Pepperkok R, Philipova RN, Kearsey SE, Ansorge W, Werner D. A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division. J Cell Sci. 1994 Jan;107 ( Pt 1):253-65. PMID:8175912
- ↑ Li J, Dong J, Wang W, Yu D, Fan X, Hui YC, Lee CSK, Lam WH, Alary N, Yang Y, Zhang Y, Zhao Q, Chen CL, Tye BK, Dang S, Zhai Y. The human pre-replication complex is an open complex. Cell. 2023 Jan 5;186(1):98-111.e21. PMID:36608662 doi:10.1016/j.cell.2022.12.008
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