Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation

Lara N. Bennett, Paul R. Clarke

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    Abstract

    Claspin is involved in ATR-dependent activation of Chk1 during DNA replication and in response to DNA damage. We show that degradation of Claspin by the ubiquitin-proteosome pathway is regulated during the cell cycle. Claspin is stabilized in S-phase but is abruptly degraded in mitosis and is absent from early G1 cells in which the phosphorylation of Chk1 by ATR is abrogated. In response to hydroxyurea, UV or aphidicolin, Claspin is phosphorylated in the Chk1-binding domain and its protein levels are increased in an ATR-dependent manner. Thus, the Chk1 pathway is regulated through both phosphorylation of Claspin and its controlled degradation.

    Original languageEnglish
    Pages (from-to)4176-4181
    Number of pages6
    JournalFEBS Letters
    Volume580
    Issue number17
    Early online date5 Jul 2006
    DOIs
    Publication statusPublished - 24 Jul 2006

    Keywords

    • ATR
    • Checkpoint
    • Chk1
    • Claspin
    • DNA damage
    • Proteolysis

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