An essential role for the Saccharomyces cerevisiae DEAD-box helicase DHH1 in G1/S DNA-damage checkpoint recovery.
The eukaryotic cell cycle displays a degree of plasticity in its regulation; cell cycle progression can be transiently arrested in response to environmental stresses. While the signaling pathways leading to cell cycle arrest are beginning to be well understood, the regulation of the release from arrest has not been well characterized. Here we show that DHH1, encoding a DEAD-box RNA helicase orthologous to the human putative proto-oncogene p54/RCK, is important in release from DNA-damage-induced cell cycle arrest at the G1/S checkpoint. DHH1 mutants are not defective for DNA repair and recover normally from the G2/M and replication checkpoints, suggesting a specific function for Dhh1p in recovery from G1/S checkpoint arrest. Dhh1p has been suggested to play a role in partitioning mRNAs between translatable and nontranslatable pools, and our results implicate this modulation of mRNA metabolism in the recovery from G1/S cell cycle arrest following DNA damage. Furthermore, the high degree of conservation between DHH1 and its human ortholog suggests that this mechanism is conserved among all eukaryotes and potentially important in human disease.
Bergkessel
Megan
M
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Reese
Joseph C
JC
D000595:Amino Acid Sequence; D002453:Cell Cycle; D002469:Cell Separation; D002471:Cell Transformation, Neoplastic; D053487:DEAD-box RNA Helicases; D004249:DNA Damage; D004260:DNA Repair; D005434:Flow Cytometry; D016193:G1 Phase; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D020365:RNA Helicases / Q000737:chemistry / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C445083:DHH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases