Human CDC25B and CDC25C differ by their ability to restore a functional checkpoint response after gene replacement in fission yeast.
In fission yeast, inactivation of the Cdc25 phosphatase by checkpoint kinases participates in the signaling cascade that temporarily stops cell cycle progression after DNA damage. In human, CDC25B and C are also known to be targeted by a similar checkpoint machinery. We have examined by homologous recombination, whether CDC25B and CDC25C were able to substitute for the function of fission yeast Cdc25. We demonstrate that (i) CDC25B and C efficiently replace Cdc25 for vegetative growth, (ii) CDC25C is able to restore a functional checkpoint in response to ionizing radiation in both a Chk1- and Cds1-dependent manner, (iii) CDC25B and C are equally efficient in the response to UV irradiation, CDC25B being only dependent on Chk1, while CDC25C depends on both Chk1 and Cds1, and (iv) CDC25C is able to restore a functional DNA replication checkpoint induced by hydroxyurea in a Cds1-dependent manner. The consequences of these findings on our current view of the checkpoint cascade are discussed.
Mondesert
Odile
O
LBCMCP-CNRS UMR5088, Université Paul Sabatier, IFR109 Institut d'Exploration Fonctionnelle des Génomes, 118 route de Narbonne, 31062 Toulouse, France.
Ducommun
Bernard
B
Bugler
Béatrix
B
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000235:genetics*; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases / Q000235:genetics* / Q000502:physiology*; D020666:ras-GRF1 / Q000235:genetics
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D020666:ras-GRF1; C517008:CDC25B protein, human; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D006918:Hydroxyurea