title: Human CDC25B and CDC25C differ by their ability to restore a functional checkpoint response after gene replacement in fission yeast.
abstract: 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.
authors.affiliation: LBCMCP-CNRS UMR5088, Université Paul Sabatier, IFR109 Institut d'Exploration Fonctionnelle des Génomes, 118 route de Narbonne, 31062 Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Mondesert
authors.forename: Bernard
authors.initials: B
authors.lastname: Ducommun
authors.forename: Béatrix
authors.initials: B
authors.lastname: Bugler
mesh_terms: 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
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D020666:ras-GRF1; C517008:CDC25B protein, human; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D006918:Hydroxyurea