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TitleStructural and mechanistic insights into the MCM8/9 helicase complex.
Journal, issue, pagesElife, Vol. 12, Year 2023
Publish dateAug 3, 2023
AuthorsZhuangfeng Weng / Jiefu Zheng / Yiyi Zhou / Zuer Lu / Yixi Wu / Dongyi Xu / Huanhuan Li / Huanhuan Liang / Yingfang Liu /
PubMed AbstractMCM8 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 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 threefold 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 MCM8/9's N-tier ring converts its symmetry from to with a conformational change that expands the MCM8/9's 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 provides a basis for understanding the DNA unwinding mechanism of MCM8/9 helicase in homologous recombination.
External linksElife / PubMed:37535404 / PubMed Central
MethodsEM (single particle)
Resolution3.67 - 3.95 Å
Structure data

EMDB-32346, PDB-7w7p:
Cryo-EM structure of gMCM8/9 helicase
Method: EM (single particle) / Resolution: 3.67 Å

EMDB-33989, PDB-7yox:
Cryo-EM structure of the N-terminal domain of hMCM8/9 and HROB
Method: EM (single particle) / Resolution: 3.95 Å

Source
  • gallus gallus (chicken)
  • homo sapiens (human)
KeywordsHYDROLASE / MCM8/9

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