Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells

作者：Ate Loonstra, Marc Vooijs, H. Berna Beverloo, Bushra Al Allak, Ellen van Drunen, Roland Kanaar, Anton J. M. Berns, Jos Jonkers · 发表于：Proceedings of the National Academy of Sciences · 年份：2001 · DOI：10.1073/pnas.161269798 · 被引用次数：606 · 研究领域：DNA Repair Mechanisms、CRISPR and Genetic Engineering、Cancer therapeutics and mechanisms

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.