INTEGRATION OF FOREIGN DNA-SEQUENCES INTO MOUSE SPERM GENOME

Mouse epididymal sperm cells have the spontaneous ability to take up e xogenous DNA. A proportion of the sperm-bound DNA is further internali zed into sperm nuclei. In this work, we have followed up the fate of t he foreign DNA upon internalization into nuclei. We have found that th e internalized plasmid DNA becomes tightly associated with the nuclear scaffold, is extensively rearranged, and undergoes recombination with the sperm genomic DNA. Sequence analysis of two randomly selected clo nes independently recovered by plasmid rescue from pSV(2)CAT plasmid-c hallenged sperm cells shows that DNA fragments from the plasmid are in tegrated into the mouse sperm genome. The sites of integration are ide ntical in both clones, suggesting that these events do not occur rando mly, but take place at preferential sites. A topoisomerase II consensu s sequence is found adjacent to one end of the integration site, sugge sting a possible role of this enzyme in the process of nonhomologous r ecombination.