Summary information and primary citation

PDB-id
9e2z
Class
replication-DNA
Method
cryo-EM (2.6 Å)
Summary
cryo-EM structure of human cmg helicase stalled at g4-containing DNA template
Reference
Batra S, Allwein B, Kumar C, Devbhandari S, Bruning JG, Bahng S, Lee CM, Marians KJ, Hite RK, Remus D (2025): "G-quadruplex-stalled eukaryotic replisome structure reveals helical inchworm DNA translocation." Science, 387, eadt1978. doi: 10.1126/science.adt1978.
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.
G4 notes
3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 3(-P-P-P)

Cartoon-block schematics in six views (download the tarball)

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List of 3 G-tetrads

 1 glyco-bond=---- sugar=---. groove=---- planarity=0.218 type=other  O+ nts=4 GGGG 1:F.DG38,1:F.DG42,1:F.DG46,1:F.DG50
 2 glyco-bond=---- sugar=-.3- groove=---- planarity=0.229 type=other  O+ nts=4 GGGG 1:F.DG39,1:F.DG43,1:F.DG47,1:F.DG51
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.464 type=bowl   O+ nts=4 GGGG 1:F.DG40,1:F.DG44,1:F.DG48,1:F.DG52

List of 1 G4-helix

In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.

Helix#1, 3 G-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---- sugar=---. groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG38,1:F.DG42,1:F.DG46,1:F.DG50
 2  glyco-bond=---- sugar=-.3- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG39,1:F.DG43,1:F.DG47,1:F.DG51
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG40,1:F.DG44,1:F.DG48,1:F.DG52
  step#1  pm(>>,forward)  area=7.61  rise=3.40 twist=34.0
  step#2  pm(>>,forward)  area=13.07 rise=3.57 twist=25.5
  strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG38,1:F.DG39,1:F.DG40
  strand#2 DNA glyco-bond=--- sugar=-.- nts=3 GGG 1:F.DG42,1:F.DG43,1:F.DG44
  strand#3 DNA glyco-bond=--- sugar=-3- nts=3 GGG 1:F.DG46,1:F.DG47,1:F.DG48
  strand#4 DNA glyco-bond=--- sugar=.-- nts=3 GGG 1:F.DG50,1:F.DG51,1:F.DG52

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2 stacking diagrams 
 1  glyco-bond=---- sugar=---. groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG38,1:F.DG42,1:F.DG46,1:F.DG50
 2  glyco-bond=---- sugar=-.3- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG39,1:F.DG43,1:F.DG47,1:F.DG51
  step#1  pm(>>,forward)  area=7.61  rise=3.40 twist=34.0

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 2  glyco-bond=---- sugar=-.3- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG39,1:F.DG43,1:F.DG47,1:F.DG51
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG40,1:F.DG44,1:F.DG48,1:F.DG52
  step#2  pm(>>,forward)  area=13.07 rise=3.57 twist=25.5

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List of 1 G4-stem

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

Stem#1, 3 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
 1  glyco-bond=---- sugar=---. groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG38,1:F.DG42,1:F.DG46,1:F.DG50
 2  glyco-bond=---- sugar=-.3- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG39,1:F.DG43,1:F.DG47,1:F.DG51
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG40,1:F.DG44,1:F.DG48,1:F.DG52
  step#1  pm(>>,forward)  area=7.61  rise=3.40 twist=34.0
  step#2  pm(>>,forward)  area=13.07 rise=3.57 twist=25.5
  strand#1  U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG38,1:F.DG39,1:F.DG40
  strand#2  U DNA glyco-bond=--- sugar=-.- nts=3 GGG 1:F.DG42,1:F.DG43,1:F.DG44
  strand#3  U DNA glyco-bond=--- sugar=-3- nts=3 GGG 1:F.DG46,1:F.DG47,1:F.DG48
  strand#4  U DNA glyco-bond=--- sugar=.-- nts=3 GGG 1:F.DG50,1:F.DG51,1:F.DG52
  loop#1 type=propeller strands=[#1,#2] nts=1 T 1:F.DT41
  loop#2 type=propeller strands=[#2,#3] nts=1 T 1:F.DT45
  loop#3 type=propeller strands=[#3,#4] nts=1 T 1:F.DT49

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