Formulated glyphosate activates the DNA-response checkpoint of the cell cycle leading to the prevention of G2/M transition.
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.
Marc
Julie
J
Station Biologique de Roscoff, Cycle Cellulaire et Développement, Unité Mer & Santé (FRE 2775), Centre National de la Recherche Scientifique and Université Pierre et Marie Curie, BP 74, 29682 Roscoff, France.
Bellé
Robert
R
Morales
Julia
J
Cormier
Patrick
P
Mulner-Lorillon
Odile
O
D000818:Animals; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D019926:Cyclin B / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003864:Depression, Chemical; D004625:Embryo, Nonmammalian; D016195:G2 Phase / Q000187:drug effects*; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D010063:Ovum / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis / Q000378:metabolism; D012617:Sea Urchins; D000097797:Glyphosate
D016203:CDC2 Protein Kinase; D019926:Cyclin B; D004247:DNA; D005998:Glycine; D006540:Herbicides; D010744:Phosphoric Monoester Hydrolases; D000097797:Glyphosate