Journal or Publishing Institution: Toxicological Sciences
Study: http://toxsci.oxfordjournals.org/content/82/2/436.full
Author(s): Marc, J., Bellé, R., Morales, J., Cormier, P. and Mulner-Lorillon, O.
Article Type: Peer Reviewed Study
Record ID: 1506
Abstract: A glyphosate containing pesticide impedes at 10 mM glyphosate the G2/M transition as judged from analysis of the first cell cycle of sea urchin development. We show that formulated glyphosate prevented dephosphorylation of Tyr 15 of the cell cycle regulator CDK1/cyclin B in vivo, the end point target of the G2/M cell cycle checkpoint. Formulated glyphosate had no direct effect on the dual specific cdc25 phosphatase activity responsible for Tyr 15 dephosphorylation. At a concentration that efficiently impeded the cell cycle, formulated glyphosate inhibited the synthesis of DNA occurring in S phase of the cell cycle. The extent of the inhibition of DNA synthesis by formulated glyphosate was correlated with the effect on the cell cycle. We conclude that formulated glyphosate’s effect on the cell cycle is exerted at the level of the DNA-response checkpoint of S phase. The resulting inhibition of CDK1/cyclin B Tyr 15 dephosphorylation leads to prevention of the G2/M transition and cell cycle progression.
Keywords: CDK1-Cyclin B, Formulated Glyphosate, Cell Cycle Checkpoint, DNA Synthesis; Cell Cycle, Cells, Cyclin B, DNA, CDC2 Protein Kinase, S Phase, Sea Urchins, DNA Chemical Synthesis, Glyphosate, Cell Cycle Checkpoint, Prevention; Glyphosate, Phosphatases, Physiological Effects of Pesticides, Regulation of Cell Cycles, Tyrosine; Animals, Western Blotting, CDC2 Protein Kinase, Cell Division, Pharmaceutical Chemistry, Chemical Depression, Nonmammalian Embryo, G2 Phase, Glycine, Herbicides, Ovum, Phosphoric Monoester Hydrolases; Metabolism, Drug Effects, Genetics, Physiology; G2 Transition, DNA-Response Checkpoint, DNA Synthesis, Formulate Glyphosate, Dual Specific CDC25, Phosphatase Activity, End Point Target, Glyphosate Effect, Sea Urchin Development, Cell Cycle Regulator CDK1 Cyclin, Cell Cycle Progression, Key Word, First Cell Cycle, CDK1 Cyclin Tyr, MM Glyphosate, Pesticide Impedes, Direct Effect, G2 Cell Cycle Checkpoint
Citation: Marc, J., Bellé, R., Morales, J., Cormier, P. and Mulner-Lorillon, O., 2004. Formulated glyphosate activates the DNA-response checkpoint of the cell cycle leading to the prevention of G2/M transition. Toxicological Sciences, 82(2), pp.436-442.
