MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis
2024

How MCM2-7 Ring Closure Affects DNA Replication

publication 10 minutes Evidence: high

Author Information

Author(s): Sarah V. Faull, Marta Barbon, Audrey Mossler, Zuanning Yuan, Lin Bai, L. Maximilian Reuter, Alberto Riera, Christian Winkler, Indiana Magdalou, Matthew Peach, Huilin Li, Christian Speck

Primary Institution: Imperial College London

Hypothesis

The study investigates how MCM2-7 ring closure and ATP hydrolysis are regulated during DNA replication.

Conclusion

Mcm4 is identified as the key ATPase that regulates pre-replicative complex formation, and defective MCM2-7 ring closure leads to complex disassembly.

Supporting Evidence

  • The study identifies Mcm4 as the key ATPase in regulating pre-RC formation.
  • Defective MCM2-7 ring closure leads to complex disassembly.
  • C5 is essential for MCM2-7 loading and ring closure.
  • Mutations in the Mcm5 C-terminus induce ATP-hydrolysis.
  • ATP-hydrolysis at the Mcm4/Mcm7 interface is crucial for MCM2-7 ring stability.

Takeaway

This study shows that a part of a protein called Mcm5 helps the MCM2-7 ring close around DNA, which is important for DNA copying. If it doesn't close properly, the process falls apart.

Methodology

The study used cryo-EM structures and biochemical assays to analyze the role of Mcm5 in MCM2-7 ring closure and ATP hydrolysis.

Limitations

The study primarily focuses on specific mutations and may not account for all possible variations in MCM2-7 function.

Statistical Information

P-Value

0.0058

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/s41467-024-55479-1

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication