Genetic manipulation of genomes with rare-cutting endonucleases

Trends Genet. 1996 Jun;12(6):224-8. doi: 10.1016/0168-9525(96)10019-6.


DNA double-strand breaks (DSBs) pose a threat to the genomic integrity of a cell. The failure to heal a break or the inappropriate repair of a break can result in the loss of genetic information and other potentially deleterious consequences, such as chromosomal translocations. Recent developments using rare-cutting endonucleases have allowed investigators to introduce one or a few DSBs into complex genomes. Such studies have begun to elucidate the complex mechanisms of nonhomologous and homologous repair used by mammalian cells to repair these lesions. A key finding is that gene targeting is stimulated two to three orders of magnitude by a DSB at the target locus. Thus, the use of rare-cutting endonucleases and the co-opting of cellular repair mechanisms might provide scientists with another tool for engineering changes into genomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • DNA / metabolism*
  • DNA Repair*
  • Endonucleases / metabolism*
  • Models, Genetic
  • Recombination, Genetic


  • DNA
  • Endonucleases