Structural and mechanistic insights into the MCM8/9 helicase complex.

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• DNA double-strand breaks are repaired by homologous recombination.
• The MCM8/9 helicase complex is crucial for this repair process.
• The precise mechanism of DNA binding and unwinding by MCM8/9 is not fully understood.

Purpose of the Study:

• To elucidate the structural basis of MCM8/9 complex function in DNA unwinding.
• To understand the role of MCM8/9 in DNA homologous recombination repair.

Main Methods:

• Cryo-electron microscopy single particle analysis.
• Structural dynamic analyses.
• Biochemical assays.

Main Results:

• The MCM8/9 complex forms a heterohexamer with a central channel for DNA.
• N-terminal OB domains with hairpins unwind duplex DNA.
• Activation by HROB induces a conformational change and alters symmetry.
• The C-tier ring exhibits rotary motion essential for unwinding.

Conclusions:

• The study provides the first structural insights into the MCM8/9 helicase mechanism.
• This work clarifies how MCM8/9 unwinds DNA during homologous recombination.
• The findings offer a foundation for understanding DNA repair processes.