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Structural mechanism of RECQ1 helicase in unfolding G-quadruplexes compared with duplex DNA.
Nucleic Acids Res, 53(17).
RECQ1, the most abundant RecQ helicase in human cells, is involved in telomeremaintenance in ALT cells and plays a critical role in maintaining genomicintegrity and stability. Here, we present five high-resolution crystal structuresthat systematically reveal a novel mechanism by which the RECQ1 helicaserecognizes and regulates G-quadruplex (G4) DNA structures. Our resultsdemonstrate that DNA binding induces intra-subunit rearrangement in RECQ1,transitioning it from a closed to an open conformation. This rearrangement altersthe stability of the dimer interface. G4 recognition and unwinding are driven bycoordinated interactions between the D1/D2 domains and the single-stranded DNA(ssDNA)-binding channel. This dual engagement aligns the G4 tetrad in a geometryfavorable for unwinding. ATP hydrolysis facilitates ssDNA translocation,positioning the β-hairpin to disrupt hydrogen bonds-unraveling G4 structures in amanner analogous to the unwinding of dsDNA. This study proposes a mechanisticmodel for RECQ1-mediated G4 unwinding and elucidates how RECQ1 recognizes andunwinds distinct DNA structures.
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