9E2Z

Cryo-EM structure of human CMG helicase stalled at G4-containing DNA template

This is a non-PDB format compatible entry.

Summary for 9E2Z

• Entry DOI: 10.2210/pdb9e2z/pdb
• EMDB information: 47473
• Descriptor: DNA replication licensing factor MCM2, DNA replication complex GINS protein SLD5, Cell division control protein 45 homolog, ... (19 entities in total)
• Functional Keywords: helicase, dna replication, cell division, fork stalling, translocation, replication, replication-dna complex, replication/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 738680.38

Authors

Allwein, B.,Batra, S.,Remus, D.,Hite, R. (deposition date: 2024-10-23, release date: 2025-03-26)

Primary citation

Batra, S.,Allwein, B.,Kumar, C.,Devbhandari, S.,Bruning, J.G.,Bahng, S.,Lee, C.M.,Marians, K.J.,Hite, R.K.,Remus, D.
G-quadruplex-stalled eukaryotic replisome structure reveals helical inchworm DNA translocation.
Science, 387:eadt1978-eadt1978, 2025

PubMed Abstract: DNA G-quadruplexes (G4s) are non-B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork collisions with preformed G4s in the parental DNA using reconstituted yeast and human replisomes. We demonstrate that a single G4 in the leading strand template is sufficient to stall replisomes by arresting the CMG helicase. Cryo-electron microscopy structures of stalled yeast and human CMG complexes reveal that the folded G4 is lodged inside the central CMG channel, arresting translocation. The G4 stabilizes the CMG at distinct translocation intermediates, suggesting an unprecedented helical inchworm mechanism for DNA translocation. These findings illuminate the eukaryotic replication fork mechanism under normal and perturbed conditions.

PubMed: 40048517
DOI: 10.1126/science.adt1978

Experimental method

ELECTRON MICROSCOPY (2.6 Å)