2. Academic Validation
  3. DNA damage-induced activation of p53 by the checkpoint kinase Chk2

DNA damage-induced activation of p53 by the checkpoint kinase Chk2

  • Science. 2000 Mar 10;287(5459):1824-7. doi: 10.1126/science.287.5459.1824.
A Hirao 1,  Y Y Kong,  S Matsuoka,  A Wakeham,  J Ruland,  H Yoshida,  D Liu,  S J Elledge,  T W Mak
Affiliations

Affiliation

  • 1 The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, M5G 2C1, Canada.
PMID: 10710310 DOI: 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 gamma-irradiation-induced arrest in the G2 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 gamma irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to gamma 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.

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