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    Poly(ADP-ribose) polymerase-1 is a survival factor for radiation-exposed intestinal epithelial stem cells in vivo.

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    Authors
    Ishizuka, Satoshi
    Martin, Kareen
    Booth, Catherine
    Potten, Christopher S
    De Murcia, Gilbert
    Bürkle, Alexander
    Kirkwood, Thomas B L
    Affiliation
    School of Clinical Medical Sciences-Gerontology, Institute for Ageing and Health, University of Newcastle upon Tyne, Newcastle upon Tyne NE4 6BE, UK.
    Issue Date
    2003-11-01
    
    Metadata
    Show full item record
    Abstract
    Poly(ADP-ribose) polymerase-1 (PARP-1) is a key enzyme mediating the cellular response to DNA strand breaks. It plays a critical role in genomic stability and survival of proliferating cells in culture undergoing DNA damage. Intestinal epithelium is the most proliferative tissue in the mammalian body and its stem cells show extreme sensitivity to low-level genotoxic stress. We investigated the role of PARP-1 in the in vivo damage response of intestinal stem cells in crypts of PARP-1-/- and control mice following whole-body gamma-irradiation (1 Gy). In the PARP-1-/- mice there was a significant delay during the first 6 h in the transient p53 accumulation in stem cells whereas an increased number of cells were positive for p21(CIP1/WAF1). Either no or only marginal differences were noted in MDM2 expression, apoptosis, induction of or recovery from mitotic blockage, or inhibition of DNA synthesis. We further observed a dose-dependent reduction in crypt survival measured at 4 days post-irradiation in control mice, and this crypt-killing effect was significantly potentiated in PARP-1-/- mice. Our results thus establish that PARP-1 acts as a survival factor for intestinal stem cells in vivo and suggest a functional link with early p53 and p21(CIP1/WAF1) responses.
    Citation
    Poly(ADP-ribose) polymerase-1 is a survival factor for radiation-exposed intestinal epithelial stem cells in vivo. 2003, 31 (21):6198-205 Nucleic Acids Res.
    Journal
    Nucleic Acids Research
    URI
    http://hdl.handle.net/10541/82355
    PubMed ID
    14576306
    Type
    Article
    Language
    en
    ISSN
    1362-4962
    Collections
    All Paterson Institute for Cancer Research

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