A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation.

ABSTRACT:

Background

The mammalian DNA-damage response (DDR) has evolved to protect genome stability and maximize cell survival following DNA-damage. One of the key regulators of the DDR is p53, itself tightly regulated by MDM2. Following double-strand DNA breaks (DSBs), mediators including ATM are recruited to the site of DNA-damage. Subsequent phosphorylation of p53 by ATM and ATM-induced CHK2 results in p53 stabilization, ultimately intensifying transcription of p53-responsive genes involved in DNA repair, cell-cycle checkpoint control and apoptosis.

Methods

In the current study, we investigated the stabilization and activation of p53 and associated DDR proteins in response to treatment of human colorectal cancer cells (HCT116p53+/+) with the MDM2 antagonist, Nutlin-3.

Results</

SUBMITTER: Valentine JM 

PROVIDER: S-EPMC3050855 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature