Summary information and primary citation

PDB-id
9ej9
Class
isomerase-DNA
Method
cryo-EM (2.8 Å)
Summary
Human fancj helicase bound to a parallel g4 DNA
Reference
You Q, Kakusho N, Sasanuma H, Masai H, Li H (2026): "Cryo-EM structures of human FANCJ reveal the mechanism of G-quadruplex unwinding and disease-associated mutations." Nat Commun. doi: 10.1038/s41467-026-75715-0.
Abstract
Guanine-rich nucleic acid sequences can fold into G-quadruplex (G4) structures that regulate DNA replication, transcription, and translation. Fanconi anemia group J helicase (FANCJ) resolves G4 structures at stalled replication forks. Despite its central role in genome maintenance, the molecular basis of G4 recognition and unwinding by FANCJ has remained unclear. Here, we report cryo-EM structures of human FANCJ bound to a G4-containing DNA substrate and ATPγS. The structures reveal direct engagement of the G4 by the Fe-S domain. Structure-guided mutagenesis demonstrates that this interface is essential for G4 binding and unwinding. The structures further capture open and closed conformational states linked to ATP hydrolysis, providing a mechanism for directional translocation along 5' ssDNA and progressive G4 unwinding. Together, these findings establish the structural basis of G4 recognition by FANCJ and provide mechanistic insights into how disease-associated mutations linked to Fanconi anemia and breast cancer impair helicase function.
G4 notes
2 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 2(-P-P-P)

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

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List of 2 G-tetrads

 1 glyco-bond=---- sugar=3.-- groove=---- planarity=0.246 type=other  O+ nts=4 GGGG B.DG17,B.DG21,B.DG26,B.DG30
 2 glyco-bond=---- sugar=---3 groove=---- planarity=0.282 type=other  O+ nts=4 GGGG B.DG18,B.DG22,B.DG27,B.DG31

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, 2 G-tetrads, INTRA-molecular, with 1 stem
 1  glyco-bond=---- sugar=3.-- groove=---- WC-->Major O+ nts=4 GGGG B.DG17,B.DG21,B.DG26,B.DG30
 2  glyco-bond=---- sugar=---3 groove=---- WC-->Major O+ nts=4 GGGG B.DG18,B.DG22,B.DG27,B.DG31
  step#1  pm(>>,forward)  area=15.89 rise=3.33 twist=30.9
  strand#1 DNA glyco-bond=-- sugar=3- nts=2 GG B.DG17,B.DG18
  strand#2 DNA glyco-bond=-- sugar=.- nts=2 GG B.DG21,B.DG22
  strand#3 DNA glyco-bond=-- sugar=-- nts=2 GG B.DG26,B.DG27
  strand#4 DNA glyco-bond=-- sugar=-3 nts=2 GG B.DG30,B.DG31

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1 stacking diagram
 1  glyco-bond=---- sugar=3.-- groove=---- WC-->Major O+ nts=4 GGGG B.DG17,B.DG21,B.DG26,B.DG30
2 glyco-bond=---- sugar=---3 groove=---- WC-->Major O+ nts=4 GGGG B.DG18,B.DG22,B.DG27,B.DG31
step#1 pm(>>,forward) area=15.89 rise=3.33 twist=30.9

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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, 2 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 2(-P-P-P)
 1  glyco-bond=---- sugar=3.-- groove=---- WC-->Major O+ nts=4 GGGG B.DG17,B.DG21,B.DG26,B.DG30
 2  glyco-bond=---- sugar=---3 groove=---- WC-->Major O+ nts=4 GGGG B.DG18,B.DG22,B.DG27,B.DG31
  step#1  pm(>>,forward)  area=15.89 rise=3.33 twist=30.9
  strand#1  U DNA glyco-bond=-- sugar=3- nts=2 GG B.DG17,B.DG18
  strand#2  U DNA glyco-bond=-- sugar=.- nts=2 GG B.DG21,B.DG22
  strand#3  U DNA glyco-bond=-- sugar=-- nts=2 GG B.DG26,B.DG27
  strand#4  U DNA glyco-bond=-- sugar=-3 nts=2 GG B.DG30,B.DG31
  loop#1 type=propeller strands=[#1,#2] nts=2 TG B.DT19,B.DG20
  loop#2 type=propeller strands=[#2,#3] nts=3 TAG B.DT23,B.DA24,B.DG25
  loop#3 type=propeller strands=[#3,#4] nts=2 TG B.DT28,B.DG29

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