Open Close
Reference
Citation
Lee, E.M., Trinh, T.T., Shim, H.J., Park, S.Y., Nguyen, T.T., Kim, M.J., Song, Y.H. (2012). Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks.  DNA Repair (Amst.) 11(9): 741--752.
FlyBase ID
FBrf0219169
Publication Type
Research paper
Abstract

ATR and Chk1 are protein kinases that perform major roles in the DNA replication checkpoint that delays entry into mitosis in response to DNA replication stress by hydroxyurea (HU) treatment. They are also activated by ionizing radiation (IR) that induces DNA double-strand breaks. Studies in human tissue culture and Xenopus egg extracts identified Claspin as a mediator that increased the activity of ATR toward Chk1. Because the in vivo functions of Claspin are not known, we generated Drosophila lines that each contained a mutated Claspin gene. Similar to the Drosophila mei-41/ATR and grp/Chk1 mutants, embryos of the Claspin mutant showed defects in checkpoint activation, which normally occurs in early embryogenesis in response to incomplete DNA replication. Additionally, Claspin mutant larvae were defective in G2 arrest after HU treatment; however, the defects were less severe than those of the mei-41/ATR and grp/Chk1 mutants. In contrast, IR-induced G2 arrest, which was severely defective in mei-41/ATR and grp/Chk1 mutants, occurred normally in the Claspin mutant. We also found that Claspin was phosphorylated in response to HU and IR treatment and a hyperphosphorylated form of Claspin was generated only after HU treatment in mei-41/ATR-dependent and tefu/ATM-independent way. In summary, our data suggest that Drosophila Claspin is required for the G2 arrest that is induced by DNA replication stress but not by DNA double-strand breaks, and this difference is probably due to distinct phosphorylation statuses.

PubMed ID
PubMed Central ID
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    DNA Repair (Amst.)
    Title
    DNA Repair
    Publication Year
    2002-
    ISBN/ISSN
    1568-7864 1568-7856
    Data From Reference
    Aberrations (2)
    Alleles (11)
    Genes (9)
    Insertions (4)
    Transgenic Constructs (2)