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Publication Abstract from PubMed

RECQ1, the most abundant RecQ helicase in human cells, is involved in telomere maintenance in ALT cells and plays a critical role in maintaining genomic integrity and stability. Here, we present five high-resolution crystal structures that systematically reveal a novel mechanism by which the RECQ1 helicase recognizes and regulates G-quadruplex (G4) DNA structures. Our results demonstrate that DNA binding induces intra-subunit rearrangement in RECQ1, transitioning it from a closed to an open conformation. This rearrangement alters the stability of the dimer interface. G4 recognition and unwinding are driven by coordinated interactions between the D1/D2 domains and the single-stranded DNA (ssDNA)-binding channel. This dual engagement aligns the G4 tetrad in a geometry favorable for unwinding. ATP hydrolysis facilitates ssDNA translocation, positioning the beta-hairpin to disrupt hydrogen bonds-unraveling G4 structures in a manner analogous to the unwinding of dsDNA. This study proposes a mechanistic model for RECQ1-mediated G4 unwinding and elucidates how RECQ1 recognizes and unwinds distinct DNA structures.

Structural mechanism of RECQ1 helicase in unfolding G-quadruplexes compared with duplex DNA.,Song ZY, Zhang X, Ai X, Huang LY, Hou XM, Fosse P, Liu NN, Mauffret O, Rety S, Xi XG Nucleic Acids Res. 2025 Sep 5;53(17):gkaf877. doi: 10.1093/nar/gkaf877. PMID:40966504^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.