The Drosophila Grp/Chk1 DNA Damage Checkpoint Controls Entry into Anaphase

It is well established that DNA damage induces checkpoint-mediated interphase arrest in higher eukaryotes, but recent studies demonstrate that DNA damage delays entry into anaphase as well. Damaged DNA in syncytial and gastrulating Drosophila embryos delays the metaphase/anaphase transition [1–6]. I...

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Bibliographic Details
Published in:Current biology 2005-02, Vol.15 (4), p.334-339
Main Authors: Royou, Anne, Macias, Hector, Sullivan, William
Format: Article
Language:English
Subjects:
Anaphase - physiology
Animals
Brain - physiology
Cell Cycle Proteins
Checkpoint Kinase 1
DNA Damage - physiology
DNA Mutational Analysis
DNA Restriction Enzymes
Drosophila - genetics
Drosophila - growth & development
Drosophila Proteins
Larva - physiology
Metaphase - physiology
Neurons - cytology
Neurons - physiology
Protein Kinases - genetics
Protein Kinases - physiology
Protein-Serine-Threonine Kinases
X-Rays
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Summary:It is well established that DNA damage induces checkpoint-mediated interphase arrest in higher eukaryotes, but recent studies demonstrate that DNA damage delays entry into anaphase as well. Damaged DNA in syncytial and gastrulating Drosophila embryos delays the metaphase/anaphase transition [1–6]. In human cultured cells, DNA damage also induces a delay in mitosis [7–9]. However, the mechanism by which DNA damage delays the anaphase onset is controversial. Some studies implicate a DNA damage checkpoint [6, 7, 10], whereas other studies invoke a spindle checkpoint [8]. To resolve this issue, we compared the effects of random DNA breaks induced by X-irradiation to site-specific I-CreI endonuclease-induced chromosome breaks on cell-cycle progression in wild-type and checkpoint-defective Drosophila neuroblasts. We found that both the BubR1 spindle checkpoint pathway and the Grp/Chk1 DNA damage checkpoint pathway are involved in delaying the metaphase/anaphase transition after extensive X-irradiation-induced DNA damage, whereas Grp/Chk1, but not BubR1, is required to delay anaphase onset in the presence of I-CreI-induced double-strand breaks. On the basis of these results, we propose that DNA damage in nonkinetochore regions produces a Grp/Chk1 DNA-damage-checkpoint-mediated delay in the metaphase/anaphase transition.
ISSN:0960-9822
1879-0445
DOI:10.1016/j.cub.2005.02.026