Repo-man controls a protein phosphatase 1-dependent threshold for DNA damage checkpoint activation.

ABSTRACT:

Background

In response to DNA damage, cells activate checkpoints to halt cell-cycle progression and prevent genomic instability. Checkpoint activation induced by DNA double-strand breaks (DSB) is dependent on the ATM kinase, a master regulator of the DNA damage response (DDR) that is activated through autophosphorylation and monomerization.

Results

Here we show that either protein phosphatase 1 or 2A is sufficient to suppress activation of the DDR and that simultaneous inhibition of both phosphatases fully activates the response. PP1-dependent DDR regulation is mediated by its chromatin-targeting subunit, Repo-Man. Studies in Xenopus egg extracts demonstrate that Repo-Man interacts with ATM and PP1 through distinct domains, leading to PP1-dependent regulation of ATM phosphor

SUBMITTER: Peng A 

PROVIDER: S-EPMC2860455 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature