S-phase-coupled apoptosis in tumor suppression
1Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. y.cho@vanderbilt.edu
Abstract:
DNA replication is essential for accurate transmission of genomic information from parental to daughter cells. DNA replication is licensed once per cell division cycle. This process is highly regulated by both positive and negative regulators. Over-replication, under-replication, as well as DNA damage in a cell all induce the activation of checkpoint control pathways such as ATM/ATR, CHK kinases, and the tumor suppressor protein p53, which provide "damage controls" via either DNA repairs or apoptosis. This review focuses on accumulating evidence, with the emphasis on recently discovered Killin, that S-phase checkpoint control is crucial for a mammalian cell to make a life and death decision in order to safeguard genome integrity.
Insights
Cell cycle checkpoints ensure genomic integrity by controlling DNA replication. This review highlights how S-phase checkpoint control, involving factors like Killin, guides cell fate decisions to prevent replication errors.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA replication ensures accurate genetic information transfer between cell generations.
- This process is tightly regulated by positive and negative factors.
- Replication errors or DNA damage trigger checkpoint pathways.
Purpose of the Study:
- To review the critical role of S-phase checkpoint control in mammalian cells.
- To emphasize the involvement of Killin in safeguarding genome integrity.
- To explore the cell's life and death decisions during replication stress.
Main Methods:
- Literature review focusing on DNA replication and checkpoint control.
- Analysis of evidence for S-phase checkpoint mechanisms.
- Examination of the role of specific proteins like Killin, ATM/ATR, CHK kinases, and p53.
Main Results:
- S-phase checkpoint activation is induced by replication stress or DNA damage.
- Checkpoint pathways, including ATM/ATR, CHK kinases, and p53, mediate damage control.
- Killin is a recently identified factor influencing these decisions.
Conclusions:
- S-phase checkpoint control is essential for maintaining mammalian genome integrity.
- Cells utilize these checkpoints to make critical life-or-death decisions.
- Understanding these pathways, including Killin's role, is vital for preventing genomic instability.
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