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    Mol Cell. 2000 Sep;6(3):649-59.

    Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage.

    Source

    Department of Genetics and Development, Columbia University, New York, NY 10032, USA.

    Abstract

    Cell cycle checkpoints lead to the inhibition of cell cycle progression following DNA damage. A cell-free system derived from Xenopus eggs has been established that reconstitutes the checkpoint pathway inhibiting DNA replication initiation. DNA containing double-strand breaks inhibits replication initiation in a dose-dependent manner. Upon checkpoint activation, a prereplicative complex is assembled that contains ORC, Cdc6, Cdc7, and MCM proteins but lacks Cdc45. The checkpoint is ATM dependent. Cdk2/CyclinE acts downstream of ATM and is downregulated by Cdk2 phosphorylation on tyrosine 15. Cdk2AF/CyclinE is refractory to checkpoint signaling, and Cdc25A overrides the checkpoint and restores DNA replication. This report provides the description of a DNA damage checkpoint pathway that prevents the onset of S phase independently of the transcriptional function of p53 in a vertebrate organism.

    PMID:
    11030344
    [PubMed - indexed for MEDLINE]

    Publication Types, MeSH Terms, Substances, Grant Support

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