Protein phosphatase 1 regulators in DNA damage signaling.

In response to DNA damaging agents and endogenous DNA lesions, human cells activate signaling cascades and repair mechanisms to help maintain genomic integrity. Phosphorylation plays a major role in DNA damage signaling, and the role of Ser/Thr kinases, including ATM, ATR, CHK1, CHK2 and DNA-PK, is particularly well documented. While these kinases have taken the center stage in DNA damage signaling until now, a role for Ser/Thr phosphatases is emerging, including Protein Phosphatase 1 (PP1). PP1 substrate specificity is regulated by its binding to a large number of different targeting subunits, and several of these have recently been identified as regulators of DNA damage responses. Here we review recent progress regarding the involvement of PP1 and its binding partners in DNA damage signaling.