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

    24 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

    Fingerprint

    Phosphorylation
    Ubiquitin
    Cell Cycle
    Chemical activation
    Cells
    Aphidicolin
    Degradation
    Hydroxyurea
    DNA
    DNA Replication
    S Phase
    Mitosis
    DNA Damage
    Proteins
    Protein Domains

    Keywords

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

    Cite this

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    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.",
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    Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation. / Bennett, Lara N.; Clarke, Paul R.

    In: FEBS Letters, Vol. 580, No. 17, 24.07.2006, p. 4176-4181.

    Research output: Contribution to journalArticle

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    AU - Bennett, Lara N.

    AU - Clarke, Paul R.

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