Claspin is phosphorylated in the Chk1-binding domain by a kinase distinct from Chk1

Lara N. Bennett, Conor Larkin, David A. Gillespie, Paul R. Clarke

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Chk1 protein kinase plays a critical role in checkpoints that restrict progression through the cell cycle if DNA replication has not been completed or DNA damage has been sustained. ATR-Dependent activation of Chk1 is mediated by Claspin. Phosphorylation of Claspin at two sites (Thr916 and Ser945 in humans) in response to DNA replication arrest or DNA damage recruits Chk1 to Claspin. Chk1 is subsequently phosphorylated by ATR and fully activated to control cell cycle progression. We show that ablation of Chk1 by siRNA in human cells or its genetic deletion in chicken DT40 cells does not prevent phosphorylation of Claspin at Thr916 (Ser911 in chicken). Chk1, however, does play other roles, possibly indirect, in the phosphorylation of Claspin and its induction. These results demonstrate that phosphorylation of Claspin within the Chk1-binding domain is catalysed by an ATR-dependent kinase distinct from Chk1. (c) 2008 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)973-976
    Number of pages4
    JournalBiochemical and Biophysical Research Communications
    Volume369
    Issue number3
    DOIs
    Publication statusPublished - 9 May 2008

    Keywords

    • chk1
    • claspin
    • cell cycle
    • checkpoint
    • protein kinase
    • DNA damage
    • REPLICATION CHECKPOINT RESPONSE
    • REPEATED PHOSPHOPEPTIDE MOTIFS
    • DNA-DAMAGE CHECKPOINT
    • PROTEIN-KINASE
    • CELL-CYCLE
    • ATR
    • ACTIVATION
    • DEGRADATION
    • RECOVERY
    • PATHWAY

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