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 revealed numerous chromosomal aberrations and an increased number of sister chromatid exchanges. Titration experiments in mouse embryo fibroblasts with a ligand-regulatable Cre-ER(T) show 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.
Loonstra
A
A
Division of Molecular Genetics and Center of Biomedical Genetics, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Vooijs
M
M
Beverloo
H B
HB
Allak
B A
BA
van Drunen
E
E
Kanaar
R
R
Berns
A
A
Jonkers
J
J
D000782:Aneuploidy; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004249:DNA Damage; D016195:G2 Phase; D019426:Integrases / Q000378:metabolism*; D008322:Mammals; D008938:Mitosis; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange; D014764:Viral Proteins / Q000378:metabolism*
D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases