Growth Inhibition and DNA Damage Induced by Cre Recombinase in Mammalian Cells

The use of Cre/loxP recombination in mammalian cells has expanded rapidly. We describe here that Cre expression in cultured mammalian cells may result in a markedly reduced proliferation and that this effect is dependent on the endonuclease activity of Cre. Chromosome analysis after Cre expression r...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-07, Vol.98 (16), p.9209-9214
Main Authors: Loonstra, Ate, Vooijs, Marc, Beverloo, H. Berna, Al Allak, Bushra, van Drunen, Ellen, Kanaar, Roland, Berns, Anton, Jonkers, Jos
Format: Article
Language:English
Subjects:
Alleles
Aneuploidy
Animals
Biological Sciences
Cell culture techniques
Cell cycle
Cell Division
Cell growth
Cell lines
Cells
Cells, Cultured
Chromosomes
Cre recombinase
Cultured cells
Deoxyribonucleic acid
DNA
DNA Damage
G2 Phase
Genetic engineering
Genetics
Integrases - metabolism
loxP protein
Mammals
Metaphase
Mitosis
Recombination, Genetic
Sister Chromatid Exchange
Toxicity
Viral Proteins - metabolism
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Summary:The use of Cre/loxP recombination in mammalian cells has expanded rapidly. We describe here that Cre expression in cultured mammalian cells may result in a markedly reduced proliferation and that this effect is dependent on the endonuclease activity of Cre. Chromosome analysis after Cre expression revealed numerous chromosomal aberrations and an increased number of sister chromatid exchanges. Titration experiments in mouse embryo fibroblasts with a ligand-regulatable Cre-ERTshow that toxicity is dependent on the level of Cre activity. Prolonged, low levels of Cre activity permit recombination without concomitant toxicity. This urges for a careful titration of Cre activity in conditional gene modification in mammalian cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.161269798