DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2
Top Cited Papers
- 10 March 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 287 (5459) , 1824-1827
- https://doi.org/10.1126/science.287.5459.1824
Abstract
Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting. Chk2 −/− embryonic stem cells failed to maintain γ-irradiation–induced arrest in the G 2 phase of the cell cycle. Chk2 −/− thymocytes were resistant to DNA damage–induced apoptosis. Chk2 −/− cells were defective for p53 stabilization and for induction of p53-dependent transcripts such as p21 in response to γ irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to γ irradiation. Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding. This provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.Keywords
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