Published online October 1, 2007
doi:10.1083/jcb.200705182
The Journal of Cell Biology, Vol. 179, No. 1, 41-52
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Kim et al.
SMK-1/PPH-4.1–mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos
Seung-Hwan Kim1,
Antonia H. Holway1,
Suzanne Wolff2,
Andrew Dillin2, and
W. Matthew Michael1
1 The Biological Laboratories, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
2 Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037
Correspondence to W. Matthew Michael: mmichael{at}fas.harvard.edu
During early embryogenesis in Caenorhabditis elegans, the ATL-1–CHK-1 (ataxia telangiectasia mutated and Rad3 related–Chk1) checkpoint controls the timing of cell division in the future germ line, or P lineage, of the animal. Activation of the CHK-1 pathway by its canonical stimulus DNA damage is actively suppressed in early embryos so that P lineage cell divisions may occur on schedule. We recently found that the rad-2 mutation alleviates this checkpoint silent DNA damage response and, by doing so, causes damage-dependent delays in early embryonic cell cycle progression and subsequent lethality. In this study, we report that mutations in the smk-1 gene cause the rad-2 phenotype. SMK-1 is a regulatory subunit of the PPH-4.1 (protein phosphatase 4) protein phosphatase, and we show that SMK-1 recruits PPH-4.1 to replicating chromatin, where it silences the CHK-1 response to DNA damage. These results identify the SMK-1–PPH-4.1 complex as a critical regulator of the CHK-1 pathway in a developmentally relevant context.
Abbreviations used in this paper: ATR, ataxia telangiectasia mutated and Rad3 related; FOXO, forkhead box O; MMS, methyl methanesulphonate; PP4, protein phosphatase 4; RNR, ribonucleotide reductase; SNP, single nucleotide polymorphism.
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