Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1
Antonio Galarreta1, Pablo Valledor1, Oscar Fernandez-Capetillo1,2
1Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
International Journal of Molecular Sciences
|August 27, 2021
Summary
Ubiquitination regulates DNA replication by controlling replisome disassembly. A proposed ubiquitin-CDK1 relay links replisome removal to cell cycle progression and has implications for cancer therapy.
Area of Science:
- Molecular Biology
- Cell Biology
- Genomics
Background:
- Post-translational modifications like ubiquitination and SUMOylation are crucial for DNA replication fidelity.
- These modifications signal for factor extraction from chromatin by the AAA ATPase VCP.
- Ubiquitination regulates DNA replication initiation, elongation, and termination.
Purpose of the Study:
- To review recent evidence on how active DNA replication prevents premature replisome ubiquitination.
- To discuss the role of ubiquitination in replisome removal for DNA repair.
- To explore the interplay between ubiquitination-mediated replisome disassembly and CDK1 activation.
Main Methods:
- Review of existing scientific literature and evidence.
- Analysis of molecular mechanisms regulating DNA replication machinery.
- Discussion of cellular signaling pathways.
Main Results:
- Active DNA replication restricts replisome ubiquitination to prevent premature disassembly.
- Ubiquitination mediates replisome removal, facilitating DNA repair.
- A ubiquitin-CDK1 relay model is proposed, where replisome disassembly promotes CDK1 activity, favoring further ubiquitination and disassembly.
Conclusions:
- Ubiquitination plays a critical role in replisome disassembly after DNA replication.
- The proposed ubiquitin-CDK1 relay is essential for the S phase to mitosis transition.
- This model offers insights into cancer therapies targeting CDK1 and inducing DNA damage.
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