Intra-S checkpoint

Definition

The intra-S checkpoint is a critical regulatory mechanism in the cell cycle that ensures the integrity of DNA during the synthesis (S) phase. This checkpoint monitors the replication of DNA, detecting any DNA damage or replication stress, and prevents the cell from progressing to the next phase until these issues are resolved. By doing so, it plays a crucial role in maintaining genomic stability and preventing the propagation of damaged DNA.

5 Must Know Facts For Your Next Test

1. The intra-S checkpoint is activated in response to DNA damage or replication stress, preventing progression to the G2 phase until issues are resolved.
2. Key proteins involved in the intra-S checkpoint include ATR (ataxia telangiectasia and Rad3 related) and Chk1 (checkpoint kinase 1), which help to halt cell cycle progression.
3. Failure of the intra-S checkpoint can lead to genomic instability, which is often implicated in cancer development.
4. The intra-S checkpoint not only halts replication but can also initiate repair processes to fix any detected DNA damage.
5. Proper functioning of the intra-S checkpoint is essential for normal cell division and organismal development, as it ensures that cells replicate their DNA accurately.

Review Questions

• How does the intra-S checkpoint contribute to maintaining genomic stability during the S phase of the cell cycle?
  • The intra-S checkpoint contributes to genomic stability by monitoring DNA replication for any damage or stress. If problems are detected, the checkpoint activates proteins like ATR and Chk1, which halt progression to the G2 phase until the issues are resolved. This mechanism prevents the duplication of damaged DNA, thereby reducing the risk of mutations that could lead to cancer or other genetic disorders.
• What roles do checkpoint kinases play in the intra-S checkpoint regulation, and how might their dysfunction impact cellular processes?
  • Checkpoint kinases such as ATR and Chk1 are crucial for regulating the intra-S checkpoint by detecting DNA damage and activating repair pathways. They initiate a signaling cascade that stops cell cycle progression if abnormalities are found. Dysfunction of these kinases can lead to unchecked cell division despite DNA damage, resulting in genomic instability and increased cancer risk due to the accumulation of mutations.
• Evaluate the significance of the intra-S checkpoint in cancer biology and potential therapeutic approaches targeting this checkpoint.
  • The intra-S checkpoint is significant in cancer biology because its failure can lead to genomic instability, a hallmark of cancerous cells. Targeting this checkpoint could provide therapeutic avenues; for example, inhibitors could be used to exploit cancer cells' reliance on these pathways for survival. By selectively impairing the intra-S checkpoint in cancer cells while sparing normal cells, researchers aim to develop treatments that reduce tumor growth while minimizing side effects on healthy tissue.

Related terms

Cell Cycle: The series of phases that a cell goes through as it grows and divides, including G1, S, G2, and M phases.

DNA Repair Mechanisms: The various processes by which a cell identifies and corrects damage to its DNA molecules, ensuring cellular integrity.

Checkpoint Kinases: A group of proteins that are activated at checkpoints during the cell cycle to monitor and respond to DNA damage or replication errors.