checkpoint kinase

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checkpoint kinase2016-10-22T14:49:10+00:00

checkpoint kinase

MOLECULAR MEDICINE

Any of a number of phosphorylation-activated serine/threonine kinases involved in controlling the cell cycle, of which there are two subtypes: Chk1 and Chk2.

checkpoint kinase image from New Medical Terms

schematic of checkpoint kinase

Caption from image DNA damage induces intracellular signaling cascades that block DNA replication and cell cycle progression. Two parallel branches, the ATR-Chk1 and ATM-Chk2 pathways are activated by different forms of damage. Cdk activity is inhibited by degradation/inhibition of Cdc25 phosphatases and by the p53-dependent induction of the p21 Cdk inhibitor. Cdk-independent events also block origin firing through inhibition of Cdk and Cdc7 kinase activity. The Tlk1 kinase which promotes Asf1-dependent chromatin assembly is also inactivated in response to DNA damage.

Reference https://www.bioscience.org/2009/v14/af/3584/figures.htm

Checkpoint kinases are essential factors which delay cell cycle progression in normal and damaged cells and can act at all three cell cycle checkpoints.* ATR kinase phosphorylates Chk1 in response to single strand DNA breaks; ATM kinase phosphorylates Chk2 in response to double strand breaks.

*G1 checkpoint, M phasen (spindle assembly checkpoint), G2 checkpoint

Checkpoint kinases phosphorylate Cdc25 phosphatase at Ser216, leading to Cdc25 sequestration in the cytoplasm–i.e., Cdc25 cannot remove the inhibitory phosphorylation on mitotic promoting factor (MPF) and entry into mitosis is prohibited.

They also play a central a role in the physiological stresses of hypoxia and reoxygenation.

Reference  http://www.genecards.org/cgi-bin/carddisp.pl?gene=CHEK2

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