Recombinase

Recombinases are enzymes that catalyze the genetic recombination. Here, there is a cleavage and rejoining of DNA fragments, resulting in the genetic diversity and allows the repair of the mutation.

Homologous recombination

Homologous recombination was first described in 1964 by Robin Holliday. It is based on the pairing of homologous extended sequences in bacteria and yeasts frequently in mammalian cells, however inefficient. This is due to the complexity and size of higher genomes and limited the possibilities of the process for targeted genetic modification of this cell type.

Site-specific recombination

Recombination of this type proceed via short recognition sites, such as those found in yeasts and phages. Since it is possible to transfer the corresponding enzymatic apparatus in mammalian cells, is a highly efficient system for genetic modification also higher cells. This approach is used increasingly in recent years.

The recombination systems most commonly used in this class are derived from the recombinases Cre ( cyclization recombination recombinase or Causes ) of phage P1 and Flp (named after the flippase activity by the yeast sequence segments invert ), from. Both enzymes belong to the integrase family of recombinases, which now consists of about 30 members. The following figure illustrates opportunities that arise from these systems. In addition, the systematic mutagenesis of the recognition sites has another type of reaction allows: the RMCE cassette exchange method, which constitutes a specific entry.

Medical importance

2007 German researchers succeeded for the first time to use a recombinase for HIV-1 infected cells. In this case the viral DNA is isolated using a modified Cre recombinase ( Tre ) from the genome of a CD4 helper cell. Whether the complete eradication of HIV-1 with the help of the Tre recombinase will actually be possible in the future as a gene therapy strategy, currently must be assessed with caution. There are a number of fundamental as well as technical problems that must be carefully analyzed and solved in the coming years.

Nevertheless, let the current research findings on at least theoretical musings to complete eradication. If eradication is not possible, at least one additional, alternative approach to HAART could be given.

Swell

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