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Vol. 14, No. 6, pp. 666-678, March 15, 2000
1 Howard Hughes Medical Institute, Department of Molecular
and Cell Biology, University of California, Berkeley, California 94720 USA; 2 Section of Molecular and Cellular Biology, University
of California, Davis, California 95616 USA
Checkpoints block cell cycle progression in eukaryotic cells exposed
to DNA damaging agents. We show that several Drosophila homologs of checkpoint genes, mei-41, grapes, and
14-3-3
, regulate a DNA damage checkpoint in the
developing eye. We have used this assay to show that the
mutagen-sensitive gene mus304 is also required for this
checkpoint. mus304 encodes a novel coiled-coil domain protein,
which is targeted to the cytoplasm. Similar to mei-41, mus304 is required for chromosome break repair and for genomic stability. mus304 animals also exhibit three developmental
defects, abnormal bristle morphology, decreased meiotic recombination, and arrested embryonic development. We suggest that these phenotypes reflect distinct developmental consequences of a single underlying checkpoint defect. Similar mechanisms may account for the puzzling array of symptoms observed in humans with mutations in the ATM tumor
suppressor gene.
[Key Words: Cell cycle; checkpoint; DNA damage; Drosophila; development]
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