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. 2000 Mar 10;287(5459):1824-7.
doi: 10.1126/science.287.5459.1824.

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

A Hirao  1 , Y Y Kong, S Matsuoka, A Wakeham, J Ruland, H Yoshida, D Liu, S J Elledge, T W Mak
Affiliations

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

A Hirao et al. Science. .

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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