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-Structure paper
Title | G-quadruplex-stalled eukaryotic replisome structure reveals helical inchworm DNA translocation. |
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Journal, issue, pages | Science, Vol. 387, Issue 6738, Page eadt1978, Year 2025 |
Publish date | Mar 7, 2025 |
![]() | Sahil Batra / Benjamin Allwein / Charanya Kumar / Sujan Devbhandari / Jan-Gert Brüning / Soon Bahng / Chong M Lee / Kenneth J Marians / Richard K Hite / Dirk Remus / ![]() |
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 ...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. |
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Methods | EM (single particle) |
Resolution | 2.41 - 4.3 Å |
Structure data | EMDB-47470, PDB-9e2w: EMDB-47471, PDB-9e2x: EMDB-47472, PDB-9e2y: EMDB-47473, PDB-9e2z: ![]() EMDB-47747: C-tier local refinement of human CMG G4 stall state ![]() EMDB-47748: N-tier local refinement of human CMG G4 stall state ![]() EMDB-47749: Cdc45-GINS local refinement of human CMG G4 stall state ![]() EMDB-47751: Yeast CMG-CTM G4 stall state 1 C-tier local refinement ![]() EMDB-47753: Yeast CMG G4 stall state 1, N-tier local refinement ![]() EMDB-47754: Yeast CMG G4 stall state 1 Cdc45-GINS local refinement ![]() EMDB-47755: Yeast CMG G4 stall state 1 Tof1-Csm3 local refinement ![]() EMDB-47757: C-tier local refinement of yeast CMG G4 stall state 2 ![]() EMDB-47758: N-tier local refinement of yeast CMG G4 stall state 2 ![]() EMDB-47759: Cdc45-GINS local refinement of yeast CMG G4 stall state 2 ![]() EMDB-47760: Tof1-Csm3 local refinement of yeast CMG G4 stall state 2 ![]() EMDB-47762: C-tier local refinement of yeast CMG G4 stall state 3 ![]() EMDB-47763: N-tier focused refinement of yeast CMG G4 stall state 3 ![]() EMDB-47764: Cdc45-GINS local refinement of yeast CMG G4 stall state 3 ![]() EMDB-47915: Consensus refinement of yeast CMG G4 stall state 2 ![]() EMDB-47916: Consensus refinement of human CMG G4 stall state ![]() EMDB-47925: Consensus refinement of yeast CMG G4 stall state 1 ![]() EMDB-47926: Consensus refinement of yeast CMG G4 stall state 3 |
Chemicals | ![]() ChemComp-ADP: ![]() ChemComp-MG: ![]() ChemComp-ZN: ![]() ChemComp-ATP: ![]() ChemComp-K: ![]() ChemComp-HOH: |
Source |
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![]() | REPLICATION/DNA / helicase / DNA replication / cell division / fork stalling / translocation / REPLICATION / REPLICATION-DNA complex |