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Updated: May 8, 2026
07:37
Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase
Published on: September 27, 2024
Structural Activation of DNA Unwinding by MCM8/9/HROB
Chuxuan Li1,2, Colin To3, Temitope M Adeleke3
1Department of BioSciences, Rice University, Houston, TX 77030, USA.
Biorxiv : the Preprint Server for Biology
|May 7, 2026
Summary
Minichromosomal maintenance (MCM8/9) proteins unwind DNA for repair. A cofactor, HROB, activates MCM8/9 by inducing structural changes, revealing its mechanism in DNA unwinding and damage repair.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Minichromosomal maintenance (MCM) proteins MCM8 and MCM9 form a complex crucial for DNA recombination and repair.
- Defects in MCM8/9 are associated with infertility, sex-specific disorders, and cancers.
- HROB is a recently identified cofactor of MCM8/9, but its role in activating the complex remains unclear.
Purpose of the Study:
- To elucidate the mechanism of MCM8/9 activation and DNA unwinding by HROB.
- To present dynamic structural insights into the MCM8/9-DNA-HROB-ATP analog complex.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine the dynamic structures.
- Structural analysis of the MCM8/9 complex in the presence of DNA, HROB, and ATP analogs.
Main Results:
- DNA binding induces a rotational rearrangement in MCM8/9, reconfiguring DNA-binding loops for engagement.
- HROB binds to both halves of the MCM8/9 heterohexamer, promoting a similar rotation before DNA binding.
- This action localizes MCM8/9 to crosslink damage sites, facilitating DNA unwinding.
Conclusions:
- A unified mechanistic model for MCM8/9 helicase function and HROB-mediated activation is proposed.
- HROB acts as a critical activator, guiding MCM8/9 to DNA damage sites and initiating unwinding.
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