G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation

• DOI: 10.1126/science.adt1978
• Publication Date: 2025-03-06T18:58:41Z
• Authors: Sahil Batra; Benjamin Allwein; Charanya Kumar; Sujan Devbhandari; Jan-Gert Brüning; Soon Bahng; Chong M. Lee; Kenneth J. Marians; Richard K. Hite; Dirk Remus
• Keywords: Replisome; G-quadruplex

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