Details

Autor(en) / Beteiligte

• Weng, Zhuangfeng
• Zheng, Jiefu
• Zhou, Yiyi
• Lu, Zuer
• Wu, Yixi
• Xu, Dongyi
• Li, Huanhuan
• Liang, Huanhuan
• Liu, Yingfang

Titel

Structural and mechanistic insights into the MCM8/9 helicase complex

Ist Teil von

• eLife, 2023-08, Vol.12

Ort / Verlag

England: eLife Sciences Publications Ltd

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.