title: Defective DNA replication and repair associated with decreases in deoxyribonucleotide pools in a mouse cell mutant with thermolabile ubiquitin-activating enzyme E1.
abstract: Upon shift-up in temperature, mouse tsFS20 mutant cells with thermolabile ubiquitin-activating enzyme E1 immediately stopped DNA replication and showed cell cycle arrest in S-phase. In contrast, when the cells were permeabilized with lysolecithin after culture at the nonpermissive temperature, they exhibited a normal level of replicative DNA synthesis in vitro. In agreement with this, intracellular pools of deoxyribonucleoside triphosphates were significantly reduced in the cells cultured at the nonpermissive temperature. Even under the permissive conditions, tsFS20 cells were more sensitive to hydroxyurea and alkylating agents, and induced less mutation than the wild-type cells. These results suggest that the ubiquitin system affects DNA replication and repair.
authors.affiliation: Laboratory of Mutagenesis, National Institute of Genetics, Yata, Mishima, 411-0801, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Aoki
authors.forename: K
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Wataya
authors.forename: S
authors.initials: S
authors.lastname: Kankawa
authors.forename: S
authors.initials: S
authors.lastname: Kaneda
authors.forename: D
authors.initials: D
authors.lastname: Ayusawa
authors.forename: T
authors.initials: T
authors.lastname: Seno
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D003854:Deoxyribonucleotides / Q000378:metabolism*; D004795:Enzyme Stability; D006918:Hydroxyurea / Q000494:pharmacology; D008025:Ligases / Q000235:genetics* / Q000378:metabolism*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D012264:Ribonucleotide Reductases / Q000378:metabolism; D013696:Temperature; D044764:Ubiquitin-Activating Enzymes; D044767:Ubiquitin-Protein Ligases
chemical_list: D003854:Deoxyribonucleotides; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D012313:RNA; D012264:Ribonucleotide Reductases; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes; D006918:Hydroxyurea