Formulated glyphosate activates the DNA-response checkpoint of the cell cycle leading to the prevention of G2/M transition

被引:40
作者
Marc, J
Bellé, R
Morales, J
Cormier, P
Mulner-Lorillon, O
机构
[1] Stn Biol Roscoff, Unite Mer & Sante, FRE 2775, F-29682 Roscoff, France
[2] Univ Paris 06, F-29682 Roscoff, France
关键词
CDK1-cyclin B; formulated glyphosate; cell cycle checkpoint; DNA synthesis;
D O I
10.1093/toxsci/kfh281
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:436 / 442
页数:7
相关论文
共 39 条
[1]   M-PHASE-SPECIFIC PROTEIN-KINASE FROM MITOTIC SEA-URCHIN EGGS - CYCLIC ACTIVATION DEPENDS ON PROTEIN-SYNTHESIS AND PHOSPHORYLATION BUT DOES NOT REQUIRE DNA OR RNA-SYNTHESIS [J].
ARION, D ;
MEIJER, L .
EXPERIMENTAL CELL RESEARCH, 1989, 183 (02) :361-375
[2]   Microtubule dependence of chromosome cycles in Xenopus laevis blastomeres under the influence of a DNA synthesis inhibitor, aphidicolin [J].
Clute, P ;
Masui, Y .
DEVELOPMENTAL BIOLOGY, 1997, 185 (01) :1-13
[3]   Regulating mammalian checkpoints through Cdc25 inactivation [J].
Donzelli, M ;
Draetta, GF .
EMBO REPORTS, 2003, 4 (07) :671-677
[4]   THE XENOPUS CDC2 PROTEIN IS A COMPONENT OF MPF, A CYTOPLASMIC REGULATOR OF MITOSIS [J].
DUNPHY, WG ;
BRIZUELA, L ;
BEACH, D ;
NEWPORT, J .
CELL, 1988, 54 (03) :423-431
[5]   Protection of DNA during early development: adaptations and evolutionary consequences [J].
Epel, D .
EVOLUTION & DEVELOPMENT, 2003, 5 (01) :83-88
[6]   CYCLIN - A PROTEIN SPECIFIED BY MATERNAL MESSENGER-RNA IN SEA-URCHIN EGGS THAT IS DESTROYED AT EACH CLEAVAGE DIVISION [J].
EVANS, T ;
ROSENTHAL, ET ;
YOUNGBLOM, J ;
DISTEL, D ;
HUNT, T .
CELL, 1983, 33 (02) :389-396
[7]   The midblastula transition in Xenopus embryos activates multiple pathways to prevent apoptosis in response to DNA damage [J].
Finkielstein, CV ;
Lewellyn, AL ;
Maller, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (03) :1006-1011
[8]   Kinetic analysis of the catalytic domain of human Cdc25B [J].
Gottlin, EB ;
Xu, X ;
Epstein, DM ;
Burke, SP ;
Eckstein, JW ;
Ballou, DP ;
Dixon, JE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) :27445-27449
[9]   Responses to DNA damage in Xenopus:: cell death or cell cycle arrest [J].
Greenwood, J ;
Costanzo, V ;
Robertson, K ;
Hensey, C ;
Gautier, J .
CELL CYCLE AND DEVELOPMENT, 2001, 237 :221-234
[10]   CHECKPOINTS - CONTROLS THAT ENSURE THE ORDER OF CELL-CYCLE EVENTS [J].
HARTWELL, LH ;
WEINERT, TA .
SCIENCE, 1989, 246 (4930) :629-634