Genetic recombination model

In this double-strand break repair model for recombination, the 3 ends are used to initiate the genetic exchange. Once paired with the complementary strand on the intact homolog, a region of hybrid DNA is created that contains complementary strands from two different parent DNAs (the product of step (2)in Fig. 25-31a). Each of the 3 ends can then act as a primer for DNA replication. The structures thus formed, Holliday intermediates (Fig. 25 31b), are a feature of homologous genetic recombination pathways in all organisms. 

Figure 23.14. A general model for double-strand break repair using homologous recombination. The text in parentheses to the right indicates proteins that participate in each step in E. coli. The light blue lines indicate newly synthesized DNA. (Reproduced with permission from Kowalczykowski, S.C. Initiation of genetic recombination and recombination-dependent replication. Trends Biochem. Sci. 25 156-165, 2000.) See color insert.

It is somewhat difficult to imagine how such a structural feat could be accomplished, but there is compelling evidence to support this recombination model. First, genetic analyses have demonstrated that genetic information is definitely exchanged between each strand. Second, DNA modifying enzymes that have the necessary functions for... 

To substantiate this concept, the present set of experiments should be complemented by analogous data from transfection experiments with phage DNAs showing single-hit kinetics due to transfection with monomeric molecules. The model would predict that in these cases transfection crosses would not yield results which are basically different from normal phage crosses. Unfortunately, 029 can not be used for this purpose. 029 DNA molecules show a tendency to aggregate (Hirokawa, unpublished). Studies of genetic recombination in the SPO 2 system are presently under way in our laboratory. 

Numerical Comparison of the Recombination Model with a Genetic Algorithm... 

Chimeric antibodies can be expressed in mammalian cells by introducing the recombinant DNA that codes for the antibody into the cells and selecting for the rare cell that has integrated the DNA into its own chromosomes and then expresses a new protein — the desired antibody. Additional genetic manipulations of the mammalian cells are then required to select cells that secrete large amounts of the recombinant protein. Following this research and development model would theoretically lead to successful monoclonal therapies, but in practice, it had never been accomplished before the IDEC team developed rituximab. 

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