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    EMBO Rep. 2010 Nov;11(11):868-75. Epub 2010 Oct 1.

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

    Landsverk HB, Mora-Bermúdez F, Landsverk OJ, Hasvold G, Naderi S, Bakke O, Ellenberg J, Collas P, Syljuåsen RG, Küntziger T.

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    Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

    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, 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.

    PMID:
    20890310
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2966950
    Free PMC Article

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