7W1Y

Human MCM double hexamer bound to natural DNA duplex (polyAT/polyTA)

This is a non-PDB format compatible entry.

Summary for 7W1Y

• Entry DOI: 10.2210/pdb7w1y/pdb
• EMDB information: 32258
• Descriptor: DNA replication licensing factor MCM2, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (12 entities in total)
• Functional Keywords: replication, cell cycle-dna complex, cell cycle/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 14
• Total formula weight: 1140056.77

Authors

Li, J.,Dong, J.,Dang, S.,Zhai, Y. (deposition date: 2021-11-21, release date: 2023-02-08, Last modification date: 2024-06-26)

Primary citation

Li, J.,Dong, J.,Wang, W.,Yu, D.,Fan, X.,Hui, Y.C.,Lee, C.S.K.,Lam, W.H.,Alary, N.,Yang, Y.,Zhang, Y.,Zhao, Q.,Chen, C.L.,Tye, B.K.,Dang, S.,Zhai, Y.
The human pre-replication complex is an open complex.
Cell, 186:98-111.e21, 2023

PubMed Abstract: 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-Å 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.

PubMed: 36608662
DOI: 10.1016/j.cell.2022.12.008

Experimental method

ELECTRON MICROSCOPY (2.59 Å)