Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Retracted Publication
MeSH terms
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / embryology*
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Caenorhabditis elegans / enzymology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Caenorhabditis elegans Proteins / physiology*
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Checkpoint Kinase 1
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Chromatin / metabolism
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DNA Damage*
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Embryo, Nonmammalian / enzymology
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Embryonic Development / genetics
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Enzyme Activation
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Longevity / genetics
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Molecular Sequence Data
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Mutation
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism
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Phosphoprotein Phosphatases / physiology*
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Protein Subunits / physiology
Substances
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Caenorhabditis elegans Proteins
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Chromatin
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Protein Subunits
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Protein Kinases
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Checkpoint Kinase 1
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chk-1 protein, C elegans
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Phosphoprotein Phosphatases
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SMK-1 protein, C elegans
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protein phosphatase 4