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ToxSci Advance Access originally published online on September 16, 2004
Toxicological Sciences 2004 82(2):436-442; doi:10.1093/toxsci/kfh281
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Toxicological Sciences vol. 82 no. 2 © Society of Toxicology 2004; all rights reserved.

Formulated Glyphosate Activates the DNA-Response Checkpoint of the Cell Cycle Leading to the Prevention of G2/M Transition

Julie Marc, Robert Bellé1, Julia Morales, Patrick Cormier and Odile Mulner-Lorillon

Station Biologique de Roscoff, Cycle Cellulaire et Développement, Unité Mer & Santé (FRE 2775), Centre National de la Recherche Scientifique (CNRS) and Université Pierre et Marie Curie (UPMC), BP 74, 29682 Roscoff, France

Received July 5, 2004; accepted September 9, 2004

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.

Key Words: CDK1-cyclin B; formulated glyphosate; cell cycle checkpoint; DNA synthesis.


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This article has been cited by other articles:


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 MutagenesisHome page
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[Abstract] [Full Text] [PDF]


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