Overexpression of cyclin E does not influence homologous recombination in Chinese hamster cells.
Overexpressed cyclin E in tumours is a prognosticator for poor patient outcome. Cells that overexpress cyclin E have been shown to be impaired in S-phase progression and exhibit genetic instability that may drive this subset of cancers. However, the origin for genetic instability caused by cyclin E overexpression is unknown. Homologous recombination plays an important role in S-phase progression and is also regulated by the same proteins that regulate cyclin E-associated kinase activity, i.e., p53 and p21. To test the hypothesis that overexpressed cyclin E causes genetic instability through homologous recombination, we investigated the effect of cyclin E overexpression on homologous recombination in the hprt gene in a Chinese hamster cell line. Although cyclin E overexpression shortened the G1 phase in the cell cycle as expected, we could see no change in neither spontaneous nor etoposide-induced recombination. Also, overexpression of cyclin E did not affect the repair of DNA double-strand breaks and failed to potentiate the cytotoxic effects of etoposide. Our data suggest that genetic instability caused by overexpression of cyclin E is not mediated by aberrant homologous recombination.
Lundin
Cecilia
C
Department of Genetic and Cellular Toxicology, Stockholm University, Stockholm, Sweden.
Samuelsson
Magnus K R
MK
Helleday
Thomas
T
D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D006224:Cricetinae; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011995:Recombination, Genetic
D019927:Cyclin E; D019384:Nucleic Acid Synthesis Inhibitors; D005047:Etoposide; D004247:DNA