What does Chk1 and Chk2 do?

The key mission of Chk1 and Chk2 is to relay the checkpoint signals from the proximal checkpoint kinases of the phosphatidylinositol 3-kinase family, particularly ATM and ATR, and likely also the newly identified ATX (Abraham, 2001, Shiloh, 2003, Kastan and Lim, 2000; and R.

What is ATM-Chk2?

The ATM kinase is crucial for the initiation of signalling pathways in mammalian cells in response to DSBs (Shiloh, 2003). One of its effector targets is Chk2, a kinase that enforces checkpoint arrest at multiple cell cycle phases (Bartek and Lukas, 2003).

What is the difference between Chk1 and Chk2?

Phosphorylated activation of Chk1 is mainly dependent on ATR, whereas Chk2 is preferred to be activated by ATM. ATR related-Chk1 pathway is usually activated by blocked replication fork progression, whereas the ATM-Chk2 pathway responds to DSB (33, 39).

Which two pathways can ATM activate?

Cellular responses to DNA damage are coordinated primarily by two distinct kinase signaling cascades, the ATM-Chk2 and ATR-Chk1 pathways, which are activated by DNA double-strand breaks (DSBs) and single-stranded DNA respectively.

How is Chk1 involved in the DNA damage response?

The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle. Chk1 activation Chk1 is regulated by ATR through phosphorylation, forming the ATR-Chk1 pathway.

How does Chk1 interact with PLK1 and Wee1 kinase?

WEE1 kinase and PLK1 are also targeted by Chk1 to induce cell cycle arrest. Phosphorylation of WEE1 kinase inhibits cdk1 which results in cell cycle arrest at the G2 phase. Chk1 has a role in the spindle checkpoint during mitosis thus interacts with spindle assembly proteins Aurora A kinase and Aurora B kinase.

What is the function of checkpoint kinase 1?

Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response.

What is the role of Chk2 in apoptosis?

Once activated, Chk2 can phosphorylate several key substrates, including Cdc25C, Cdc25A, p53, Brca1, the promyleocytic leukemia protein (PML), and E2F-1, which is required to mediate cell cycle arrest, DNA repair, and apoptosis ( 2–4 ).