DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2
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- Teacher spread
- 0.256 · how far apart the two teachers sit on this one work
- Validation status
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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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Science
- Topic
- Cancer-related Molecular Pathways
- Field
- Medicine
- Canadian institutions
- Ontario Institute for Cancer Research
- Funders
- National Institute of General Medical Sciences
- Keywords
- Checkpoint Kinase 2DNA damageCHEK1Cell cycle checkpointG2-M DNA damage checkpointCell biologyBiologyDNA repairDNACell cycleMolecular biologyApoptosisBiochemistry
- Has abstract in OpenAlex
- yes