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bioRxiv · 10.1101/2022.01.26.477944

Molecular insights into the MCM8/9 helicase complex in DNA unwinding and translocation

Weng, Z.·Li, J.·Zheng, J.·Li, H.·Lu, Z.·Zhou, Y.·Xu, D.·Liang, H.·Liu, Y.
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Abstract

MCM8 and MCM9 form a functional helicase complex (MCM8/9) that plays an essential role in DNA homologous recombination repair for DNA double-strand break. However, the structural characterization of MCM8/9 for DNA binding/unwinding remains unclear. Here, we report structures of the MCM8/9 complex using cryo-electron microscopy single particle analysis. The structures reveal that MCM8/9 is arranged into a heterohexamer through a three-fold symmetry axis, creating a central channel that accommodates DNA. Multiple characteristic hairpins from the N-terminal oligosaccharide/oligonucleotide (OB) domains of MCM8/9 protrude into the central channel and serve to unwind the duplex DNA. When activated by HROB, the structure of MCM8/9s N-tier ring converts its symmetry from C3 to C1 with a conformational change that expands the MCM8/9s trimer interface. Moreover, our structural dynamic analyses revealed that the flexible C-tier ring exhibited rotary motions relative to the N-tier ring, which is required for the unwinding ability of MCM8/9. In summary, our structural and biochemistry study provide a basis for understanding the DNA unwinding mechanism of MCM8/9 helicase in homologous recombination.

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Weng, Z., Li, J., Zheng, J., Li, H., Lu, Z., Zhou, Y., Xu, D., Liang, H., Liu, Y.. 2022-01-27. Molecular insights into the MCM8/9 helicase complex in DNA unwinding and translocation. https://doi.org/10.1101/2022.01.26.477944

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