Tof1p regulates DNA damage responses during S phase in Saccharomyces cerevisiae.
A tof1 mutant was recovered in a screen aimed at identifying genes involved specifically in the S phase branch of the MEC1-dependent DNA damage response pathway. The screen was based on the observation that mutants missing this branch are particularly dependent on the cell cycle-wide branch and, therefore, on RAD9, for surviving DNA damage. tof1 and rad9 conferred synergistic sensitivity to MMS, UV, and HU, and the double mutant was incapable of slowing S phase in response to MMS, inducing RNR3 transcription in response to UV, and phosphorylating Rad53p in response to HU. TOF1's contribution to DNA damage response appeared to be restricted to S phase, since TOF1 did not contribute to UV-induced transcription during G1 or to the cdc13-1-induced block to anaphase in G2/M. I suggest a model in which Tof1p functions to link Mec1p with Rad53p.
Foss
E J
EJ
Division of Basic Sciences, A3-023, Fred Hutchinson Cancer Research Center, 1100 Faiorview Ave., Seattle, WA 98109-1024, USA. efoss@fred.fhcrc.org
D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division; D064447:Checkpoint Kinase 2; D019926:Cyclin B / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D006918:Hydroxyurea; D047908:Intracellular Signaling Peptides and Proteins; D008741:Methyl Methanesulfonate; D008957:Models, Genetic; D009153:Mutagens; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D016196:S Phase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D019926:Cyclin B; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; C119636:TOF1 protein, S cerevisiae; C069930:rad9 protein; D008741:Methyl Methanesulfonate; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D006918:Hydroxyurea