WRN or telomerase constructs reverse 4-nitroquinoline 1-oxide sensitivity in transformed Werner syndrome fibroblasts.
WRN encodes a RecQ helicase, which is mutated in Werner syndrome. Werner syndrome is a genetic condition of young adults characterized by premature aging, limited replicative capacity of cells in vitro, and increased cancer risk. Telomerase is a reverse transcriptase that extends the G-rich strand of telomeric DNA. Primary cells in vitro typically lack telomerase activity and undergo senescence, whereas telomerase is reactivated in many, but not all, tumors. The roles of the two genes are not known to be related. Here we report the development of an effective colony-forming assay in which a SV40-transformed Werner fibroblast cell line is 6-18-fold more sensitive to 4-nitroquinoline 1-oxide than SV40-transformed normal cell lines. The sensitivity can be partially reversed by transfecting a normal WRN gene but not a mutated WRN gene into the cells. Curiously, the sensitivity can be reversed equally well by transfecting a telomerase gene (TERT) into the cells. These data indicate the possibility of an interdependent function of these two genes.
Hisama
F M
FM
Boyer Center for Molecular Medicine, Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Chen
Y H
YH
Meyn
M S
MS
Oshima
J
J
Weissman
S M
SM
D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002461:Cell Line, Transformed; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005090:Exodeoxyribonucleases; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009153:Mutagens / Q000378:metabolism*; D009154:Mutation; D012313:RNA; D053484:RecQ Helicases; D017422:Sequence Analysis, DNA; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics; D014162:Transfection; D014898:Werner Syndrome / Q000201:enzymology* / Q000235:genetics; D000071657:Werner Syndrome Helicase
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009153:Mutagens; C422952:telomerase RNA; D015112:4-Nitroquinoline-1-oxide; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase