Defective DNA Replication and Repair Associated with Decreases in Deoxyribonucleotide Pools in a Mouse Cell Mutant with Thermolabile Ubiquitin-Activating Enzyme E 1

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Upon shift-up in temperature, mouse tsFS 20 mutant cells with thermolabile ubiquitinactivating enzyme E 1 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 repliative 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, tsFS 20 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.