title: Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by expressing an hTERT gene.
abstract: Werner syndrome (WS) is an autosomal recessive disease characterized by premature aging and caused by mutations of the WRN gene mapped at 8p12. To examine functional complementation of WS phenotypes, we introduced a normal human chromosome 8 into a strain of WS fibroblasts (WS3RGB) immortalized by expressing a human telomerase reverse transcriptase subunit (hTERT) gene. Here, we demonstrate that the abnormal WS phenotypes including cellular sensitivities to 4-nitroquinoline-1-oxide (4NQO) and hydroxy urea (HU), and chromosomal radiosensitivity at G(2) phase are corrected by expression of the WRN gene mediated by introducing a chromosome 8. This indicates that those multiple abnormal WS phenotypes are derived from a primary, but not secondary, defect in the WRN gene.
authors.affiliation: Radiation Biology Laboratory, Radiation Research Center, Frontier Science Innovation Center, Organization for University-Industry-Government Cooperation, Osaka Prefecture University, Sakai, Osaka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Goto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.forename: Kanji
authors.initials: K
authors.lastname: Ishizaki
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Seiji
authors.initials: S
authors.lastname: Kodama
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002461:Cell Line, Transformed; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts; D016195:G2 Phase; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: D015112:4-Nitroquinoline-1-oxide; C509186:TERT protein, human; D019098:Telomerase; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase