9ej9

Human FANCJ helicase bound to a parallel G4 DNA

spinqualitylabelsall models 9ej9, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ej9 is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.8Å Ligands: AGS, K, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FANCJ_HUMAN Defects in BRIP1 are a cause of susceptibility to breast cancer (BC) [MIM:114480. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Defects in BRIP1 are the cause of Fanconi anemia complementation group J (FANCJ) [MIM:609054. It is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Function FANCJ_HUMAN DNA-dependent ATPase and 5' to 3' DNA helicase required for the maintenance of chromosomal stability. Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination. Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1. Publication Abstract from PubMed 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 ATPgammaS. 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. Cryo-EM structures of human FANCJ reveal the mechanism of G-quadruplex unwinding and disease-associated mutations.,You Q, Kakusho N, Sasanuma H, Masai H, Li H Nat Commun. 2026 Jul 15. doi: 10.1038/s41467-026-75715-0. PMID:42457705 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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