9e2y
Cryo-EM structure of yeast CMG helicase stalled at G4-containing DNA template, state 3
Structural highlights
FunctionMCM7_YEAST Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.[1] [2] Publication Abstract from PubMedDNA 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. G-quadruplex-stalled eukaryotic replisome structure reveals helical inchworm DNA translocation.,Batra S, Allwein B, Kumar C, Devbhandari S, Bruning JG, Bahng S, Lee CM, Marians KJ, Hite RK, Remus D Science. 2025 Mar 7;387(6738):eadt1978. doi: 10.1126/science.adt1978. Epub 2025 , Mar 7. PMID:40048517[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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