Cdc7 kinases (DDKs) and checkpoint responses: lessons from two yeasts.
Principally characterized for its requirement in the initiation of DNA replication, compelling evidence from two yeast model organisms now points to a central role for the Dbf4/Cdc7 kinase complex in S-phase checkpoint responses. Among the key findings supporting this view are observations that orthologs Dfp1 (Schizosaccharomyces pombe) and Dbf4 (Saccharomyces cerevisiae) interact with equivalent checkpoint kinases Cds1 and Rad53, respectively, and that mutants for Dbf4 and Cdc7 in these species are sensitive to genotoxic agents. Recently, these findings have been extended through mutational analyses of conserved regions in both Dfp1 and Dbf4, leading to the identification of distinct motifs which mediate cellular responses to DNA damage and replication fork arrest. The present review is a comparative survey of data obtained from studies conducted with S. pombe and S. cerevisae, and a consideration of models for the role played by Dbf4/Cdc7 in checkpoint responses.
Duncker
Bernard P
BP
Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada. bduncker@sciborg.uwaterloo.ca
Brown
Grant W
GW
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D008938:Mitosis / Q000187:drug effects; D009154:Mutation; D010750:Phosphoproteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D016196:S Phase / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D012568:Schizosaccharomyces / Q000187:drug effects / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000502:physiology; D029867:Xenopus Proteins; D014982:Xenopus laevis
D018906:Antineoplastic Agents, Alkylating; D018797:Cell Cycle Proteins; C088096:Dbf4 protein, S cerevisiae; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D029867:Xenopus Proteins; C489404:CDC7 protein, S cerevisiae; C489405:CDC7 protein, Xenopus; C489406:cdc7 protein, S pombe; D017346:Protein Serine-Threonine Kinases