The protein phosphatase 1 regulator PNUTS is a new component of the DNA damage response

The function of protein phosphatase 1 nuclear‐targeting subunit (PNUTS)—one of the most abundant nuclear‐targeting subunits of protein phosphatase 1 (PP1c)—remains largely uncharacterized. We show that PNUTS depletion by small interfering RNA activates a G2 checkpoint in unperturbed cells and prolongs G2 checkpoint and Chk1 activation after ionizing‐radiation‐induced DNA damage. Overexpression of PNUTS–enhanced green fluorescent protein (EGFP)—which is rapidly and transiently recruited at DNA damage sites—inhibits G2 arrest. Finally, γH2AX, p53‐binding protein 1, replication protein A and Rad51 foci are present for a prolonged period and clonogenic survival is decreased in PNUTS‐depleted cells after ionizing radiation treatment. We identify the PP1c regulatory subunit PNUTS as a new and integral component of the DNA damage response involved in DNA repair. This report identifies the PP1c regulatory subunit PNUTS as a novel and integral component of the DNA damage response involved in DNA repair.