I am trying to identify the exact mechanisms , in which a plasmid get incorporated into the DNA of mammalian cell , during transfection . From literature review I found it is associated with deliberate double stranded breaks during mitosis, but can't identify the mechanisms in which the Plasmid DNA is inserted. A bit of context , I am talking about non-specific site integration.
A linear DNA/linear plasmid DNA may be integrated non specifically and without homology, by Non Homologous End Joining (NHEJ) while repairing a Double strand Break (DSB) in the genomic DNA. DNA damage and repair are on-going and dynamic processes of the cell, just imagine a DSB occurs in the genome, while repairing the cellular machinery finds your linear DNA in vicinity and voila, it will be integrated by NHEJ. But the condition is, plasmid should be linear not circular. If it is circular it will be maintained as episome and will be lost during multiplications/cell expansion.
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