S-phase-coupled apoptosis in tumor suppression

Yong-Jig Cho1, Peng Liang

  • 1Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. y.cho@vanderbilt.edu

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.

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...