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Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication
FuJung Chang1, Alberto Riera2, Cecile Evrin2
1Van Andel Research Institute, Grand Rapids, United States.
Elife
|August 26, 2015
Summary
Cdc6 ATP hydrolysis is crucial for initiating DNA replication, not MCM loading. This hydrolysis enables Cdc6 to detach from the pre-replicative complex, allowing DNA replication to proceed.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- DNA replication initiation requires pre-replicative complex (pre-RC) assembly, involving MCM helicase loading.
- The precise role of Cdc6 ATP hydrolysis in this process remains unclear.
Purpose of the Study:
- To elucidate the mechanistic role of Cdc6 ATP hydrolysis in DNA replication initiation and MCM loading.
Main Methods:
- Utilized purified proteins and ATPase-defective Cdc6 mutants (e.g., Cdc6-E224Q).
- Investigated MCM loading and binding in vitro and in vivo.
- Observed cell-cycle progression and DNA replication following MCM loading.
Main Results:
- Cdc6 ATP hydrolysis is essential for initiating DNA replication but not for MCM loading.
- An ATPase-defective Cdc6 mutant facilitated MCM loading and origin binding but blocked cells in G1-phase.
- Degradation of the mutant Cdc6 allowed cells to enter S-phase and replicate DNA.
Conclusions:
- Cdc6 ATP hydrolysis is required for Cdc6 disengagement from the pre-RC post-helicase loading.
- This disengagement is critical for advancing subsequent helicase activation steps in vivo.
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