| RRC ID |
39264
|
| Author |
Kodama S, Kashino G, Suzuki K, Takatsuji T, Okumura Y, Oshimura M, Watanabe M, Barrett JC.
|
| Title |
Failure to complement abnormal phenotypes of simian virus 40-transformed Werner syndrome cells by introduction of a normal human chromosome 8.
|
| Journal |
Cancer Res
|
| Abstract |
The Werner syndrome (WS) gene (WRN) was isolated by positional cloning, based on mapping to chromosome 8p12, and the WRN protein was recently shown to encode an active helicase. To examine functional complementation of WS phenotypes by expression of the WRN gene, we introduced a normal human chromosome 8 into a SV40-transformed WS fibroblastoid cell line (WS780) by microcell fusion and studied several cellular phenotypes associated previously with WS cell lines, including cell growth rate, 4-nitroquinoline-1-oxide (4NQO) sensitivity, and spontaneous mutation rate and type of mutation at the hypoxanthine-guanine phosphoribosyl transferase locus. The WRN gene was expressed in two of three microcell hybrids introduced with chromosome 8. We failed to observe a difference between normal and WS cell lines in terms of growth rates and spontaneous mutation rates. However, we found that the WS cell line was highly sensitive to 4NQO-induced cytotoxicity and showed an unusually high proportion of deletion mutations at the hypoxanthine-guanine phosphoribosyl transferase locus as compared to a control cell line, as shown previously. Here, we report that these phenotypes were not corrected by introduction of the WRN gene, although the WRN protein was expressed. Our results suggest that the hypersensitivity to 4NQO and the extensive deletion mutations observed in the WS cell line are caused by a defect that is secondary to the WRN gene mutation, possibly a repair gene defect that controls the phenotypes of hypersensitivity to carcinogen(s) and/or the extensive deletion mutations.
|
| Volume |
58(22)
|
| Pages |
5188-95
|
| Published |
1998-11-15
|
| PMID |
9823331
|
| MeSH |
4-Nitroquinoline-1-oxide / pharmacology
Animals
Carcinogens / pharmacology
Cell Fusion
Cell Line, Transformed / drug effects
Cell Transformation, Viral
Chromosomes, Human, Pair 8 / genetics*
Chromosomes, Human, Pair 9 / genetics
DNA Helicases / genetics*
DNA Helicases / metabolism
Exodeoxyribonucleases
Gene Deletion
Genetic Complementation Test / methods
Humans
Hypoxanthine Phosphoribosyltransferase / genetics*
Mice
Microsatellite Repeats / genetics
Mutation
Phenotype
Polymorphism, Genetic
RecQ Helicases
Simian virus 40
Werner Syndrome / genetics*
Werner Syndrome / pathology
Werner Syndrome Helicase
|
| IF |
9.727
|
| Times Cited |
21
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
PSV811(RCB0223)
W-V(RCB0252) |
