Atr kinase

Definition

ATR kinase, or Ataxia Telangiectasia and Rad3-related kinase, is a crucial protein involved in the cellular response to DNA damage and stress signals. It plays a key role in the activation of cell cycle checkpoints, particularly in response to DNA damage, ensuring that cells do not progress through the cell cycle until the damage is repaired. By phosphorylating various substrates, ATR kinase coordinates repair mechanisms, signaling pathways, and cell cycle regulation.

5 Must Know Facts For Your Next Test

1. ATR kinase is primarily activated by single-stranded DNA (ssDNA) that forms during DNA replication stress or in response to DNA damage.
2. Once activated, ATR kinase phosphorylates several key proteins, including Chk1, which helps to halt cell cycle progression to allow for DNA repair.
3. ATR kinase works in conjunction with ATM (Ataxia Telangiectasia Mutated) kinase, which responds to double-stranded breaks in DNA.
4. Deficiencies in ATR kinase function can lead to increased sensitivity to DNA-damaging agents and contribute to cancer progression.
5. In addition to its role in DNA repair, ATR kinase also influences other cellular processes such as apoptosis and senescence.

Review Questions

• How does ATR kinase respond to DNA damage and what role does it play in cell cycle regulation?
  • ATR kinase responds to DNA damage primarily by recognizing single-stranded DNA that forms during replication stress. Upon activation, it plays a vital role in regulating the cell cycle by phosphorylating proteins like Chk1, which helps arrest the cell cycle at specific checkpoints. This pause allows the cell time to repair any damage before proceeding with division, thus maintaining genomic stability.
• Compare the functions of ATR kinase and ATM kinase in the context of cellular responses to DNA damage.
  • ATR kinase and ATM kinase are both crucial for responding to DNA damage but have distinct roles. ATR primarily responds to single-stranded DNA damage that occurs during replication stress, while ATM is activated by double-stranded breaks in DNA. Both kinases phosphorylate downstream targets to initiate cell cycle arrest and facilitate repair mechanisms; however, their activation pathways and specific target substrates differ according to the type of DNA damage they encounter.
• Evaluate the potential implications of ATR kinase dysfunction in cancer biology and treatment strategies.
  • Dysfunction of ATR kinase can significantly impact cancer biology by compromising the cellular ability to respond to DNA damage. This impairment may lead to genomic instability and increased mutation rates, contributing to cancer progression. In terms of treatment strategies, targeting ATR kinase could provide a novel approach for sensitizing cancer cells to DNA-damaging therapies or enhancing the effectiveness of existing treatments by exploiting the cancer cells' compromised repair pathways.

Related terms

DNA damage response: A complex network of cellular pathways that detect and repair DNA damage, ensuring genomic stability and preventing mutations.

Checkpoint kinases: Proteins that help regulate the cell cycle by detecting DNA damage and pausing cell division until the damage is resolved.

Phosphorylation:

A biochemical process that involves adding a phosphate group to a protein, which can alter the protein's function and activity.