Negative regulation of CHK2 activity by protein phosphatase 2A is modulated by DNA damage.

ABSTRACT: Checkpoint kinase 2 (CHK2) is a major effector of the DNA damage response pathway and although its mechanism of activation has been well studied, the attenuation of its activity following DNA damage has not been explored. Here, we identify the B'alpha subunit of protein phosphatase 2A (PP 2A) as a CHK2 binding partner and show that their interaction is modulated by DNA damage. B'alpha binds to the SQ/TQ repeat region of CHK2, which is a target of ATM phosphorylation. The induction of DNA double-strand breaks by gamma irradiation as well as treatment with doxorubicin causes dissociation of the B'alpha and CHK2 proteins. This dissociation correlates with an increase in the ATM-dependent phosphorylation of CHK2 at serines 33 and 35 in the SQ/TQ region. Indeed, mutating these sites to mimic ph

SUBMITTER: Freeman AK 

PROVIDER: S-EPMC3040716 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature