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Curr Opin Cell Biol. 2009 Apr;21(2):245-55. doi: 10.1016/j.ceb.2009.01.018. Epub 2009 Feb 21.

Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2.

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  • 1David H Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

In response to DNA damage eukaryotic cells activate cell cycle checkpoints -- complex kinase signaling networks that prevent further progression through the cell cycle. Parallel to implementing a cell cycle arrest, checkpoint signaling also mediates the recruitment of DNA repair pathways. If the extent of damage exceeds repair capacity, additional signaling cascades are activated to ensure elimination of these damaged cells. The DNA damage response has traditionally been divided into two major kinase branches. The ATM/Chk2 module is activated after DNA double strand breaks and the ATR/Chk1 pathway responds primarily to DNA single strand breaks or bulky lesions. Both pathways converge on Cdc25, a positive regulator of cell cycle progression, which is inhibited by Chk1-mediated or Chk2-mediated phosphorylation. Recently a third effector kinase complex consisting of p38MAPK and MK2 has emerged. This pathway is activated downstream of ATM and ATR in response to DNA damage. MK2 has been shown to share substrate homology with both Chk1 and Chk2. Here we will discuss recent advances in our understanding of the eukaryotic DNA damage response with emphasis on the Chk1, Chk2, and the newly emerged effector kinases p38MAPK and MK2.

PMID:
19230643
[PubMed - indexed for MEDLINE]
PMCID:
PMC2699687
Free PMC Article

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