9XZK

Cryo-EM structure of F-box helicase 1 (FBH1) bound to an SCF ubiquitin ligase complex and a 3-way DNA fork (head structure)

Summary for 9XZK

• Entry DOI: 10.2210/pdb9xzk/pdb
• Related: 9XZJ 9XZL 9XZM
• EMDB information: 72359
• Descriptor: Cullin-1, E3 ubiquitin-protein ligase RBX1 (2 entities in total)
• Functional Keywords: helicase, translocase, fork remodeler, fork reversal, replication fork, dna binding, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 102090.28

Authors

Mullins, E.A.,Schiltz, C.J.,Eichman, B.F. (deposition date: 2025-08-27, release date: 2026-01-28, Last modification date: 2026-03-11)

Primary citation

Greer, B.H.,Mendia-Garcia, J.,Mullins, E.A.,Peacock, E.M.,Haigh, S.K.,Schiltz, C.J.,Aicart-Ramos, C.,Tsai, M.S.,Cortez, D.,Moreno-Herrero, F.,Eichman, B.F.
Structural basis for fork reversal and RAD51 regulation by the SCF ubiquitin ligase complex of F-box helicase 1.
Nat Commun, 17:-, 2026

PubMed Abstract: Replication fork reversal helps maintain genomic stability during replication stress. F-box helicase 1 (FBH1) catalyzes fork reversal and is an SCF (SKP-CUL1-F-box) E3 ubiquitin ligase that limits RAD51 association with chromatin. Here, we show that preferential binding of SCF to the lagging strand template at DNA fork structures stimulates helicase activity and is required for fork reversal. A cryo-EM structure of SCF bound to DNA representing a stalled fork reveals an intimate interaction between FBH1 and the fork junction. Disruption of this interface severely curtails fork reversal in vitro and replication progression in cells, providing a model for how ssDNA translocation by FBH1 facilitates annealing of parental DNA by a fundamentally different mechanism than the fork remodelers SMARCAL, HLTF, and ZRANB3. The structure provides a model for SCF disassembly of RAD51 filaments through translocation and ubiquitination, and implies that RAD51 is associated with the lagging strand at stalled forks.

PubMed: 41587991
DOI: 10.1038/s41467-026-68752-2

Experimental method

ELECTRON MICROSCOPY (3.91 Å)