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

Abstract

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, 3H2AX, 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. © 2010 European Molecular Biology Organization.