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    Biochem Biophys Res Commun. 2007 Mar 23;354(4):1028-33. Epub 2007 Jan 25.

    Linking PCNA-dependent replication and ATR by human Claspin.

    Brondello JM, Ducommun B, Fernandez A, Lamb NJ.

    Source

    INSERM EMI 0229 Génotypes et Phénotypes Tumoraux CRLC Val d'Aurelle, 34298 Montpellier, Cedex 5, France. jmbrondello@valdorel.fnclcc.fr

    Abstract

    Recent studies in Xenopus have identified a new checkpoint protein called Claspin that is believed to transduce the checkpoint DNA damage signals to Chk1 kinase. Here we show that the human Claspin homolog is a chromatin bound protein either in the absence or in the presence of damaged DNA, independent of its association with ATR. Furthermore, we show that human Claspin is found in complex with PCNA, an essential component of the DNA replication machinery, and is released upon DNA replication arrest. Interfering with PCNA function by overexpression of p21 mutant, impaired in its interaction with Cdks but not with PCNA, leads to ATR-dependent Chk1 activation. These findings suggest that the dissociation of Claspin-PCNA could be part of the signal leading to Chk1 activation.

    PMID:
    17274954
    [PubMed - indexed for MEDLINE]

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