title: Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions.
abstract: Rad18 plays a crucial role in postreplication repair in both lower eukaryotes and higher eukaryotes. However, regulation of the Rad18 expression in higher eukaryotes is largely unknown. We found that the RAD18 transcript is expressed ubiquitously in various tissues and very highly in the testis in mammals. Although human RAD18 (hRAD18) transcription levels fluctuate during the cell cycle, being maximal in the late S and minimal in the early G1, the protein levels remain constant throughout the cell cycle. Following UV-irradiation, hRAD18 transcription levels decrease significantly, but Rad18 protein levels change little. The protein levels are maintained at least in part by enhanced translation rates. hRad18 localizes in the nucleus in two forms: a diffused form and a condensed form forming nuclear dots. These nuclear dots disperse rapidly in the nucleoplasm after treatments with various genotoxic agents, resulting in an enhancement of the intranuclear Rad18 concentration of the diffused form. No de novo protein synthesis is required for this process. These results suggest that in higher eukaryotes, the maintenance and dynamic translocation of Rad18 protein is important for postreplication repair.
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862-0976, Japan.
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Masuyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tateishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yomogida
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Nishimune
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakuraba
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Michio
authors.initials: M
authors.lastname: Ogawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Yamaizumi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D009492:Neurospora crassa; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; C485954:RAD18 protein, human; D012333:RNA, Messenger; D003513:Cycloheximide; D044767:Ubiquitin-Protein Ligases; D006918:Hydroxyurea