Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by expressing an hTERT gene.
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.
Ariyoshi
Kentaro
K
Radiation Biology Laboratory, Radiation Research Center, Frontier Science Innovation Center, Organization for University-Industry-Government Cooperation, Osaka Prefecture University, Sakai, Osaka, Japan.
Suzuki
Keiji
K
Goto
Makoto
M
Oshimura
Mitsuo
M
Ishizaki
Kanji
K
Watanabe
Masami
M
Kodama
Seiji
S
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
D015112:4-Nitroquinoline-1-oxide; C509186:TERT protein, human; D019098:Telomerase; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase