Biochemistry - Chemical Reactions in Living Cells, Volume 3 - D. Metzler 1980

Biochemical Genetics and the Synthesis of Nucleic Acids and Proteins
Recombination, Integration, and Excision
DNA Integration and Excision

The temperate bacteriophage λ, along with bacterial F and R factors, are all capable of integrating into cellular DNA. This process involves the Cleavage of genes, meaning that chemically it resembles recombination. However, in the case of phage λ, both the int and xis genes are required for DNA integration and excision; these genes differ from the rec locus of the bacterial Cell and from the phage's general recombination (rec) Gene. Nevertheless, chemically speaking, these processes also bear a striking similarity to recombination.

In rare instances, when phage λ is excised from the bacterial chromosome, host cell genes are found within its genome. For example, strains of phage λ have been isolated that carry genes responsible for galactase Catabolism (gal; Fig. 15-1) and biotin synthesis (bio). The ability to transfer these genes into other bacterial strains via transducing phages has significantly accelerated the mapping of bacterial Chromosomes. The map shown in Fig. 15-1 was constructed using the transducing phage P1, which is capable of inserting into the chromosome at least ten different sites. Many of the distances indicated on the map were calculated from data on the cotransfer frequencies of closely linked markers.

Unlike phage λ, which integrates into the E. coli genome at a specific site, the transducing phage Mu can insert at virtually any Location (Section D, 2). However, the phage genome contains a fixed site where the Cleavage of the circular viral DNA occurs. Insertion of an entire genome of one bacterial plasmid into a palindromic region of another plasmid has also been observed [233]. In many cases, it turns out that the same palindromic sequence—often quite long (700–1400 Base Pairs)—is present in both the plasmid and the bacterial chromosome. For instance, insertion sequences IS1, IS2, and IS3 mediate the integration of E. coli plasmid DNA into the gal and lac operons of the E. coli chromosome [233a–c]. It has been suggested that

plasmid DNA translocation is driven by Enzymes that resemble Restriction Endonucleases and exhibit site Specificity. The same mechanism may underlie Site-Specific Recombination.

It has been known for many years that genes and even entire chromosomal segments in higher organisms can occasionally shift from one location to another. In maize, "controlling elements" move from one site to another, altering Gene Expression and behaving similarly to integration-competent bacterial Plasmids [233c]. It is quite possible that this phenomenon is related to the presence of A large number of long palindromic sequences in eukaryotic DNA [235a].

The ease with which foreign DNA integrates into bacterial chromosomes is remarkable. Does the same thing happen in The Human Body? The answer is yes. However, the extent to which human Cells are resistant to changes caused by viral integration remains unclear. We know that tumor-causing (oncogenic) Viruses can incorporate into The Genome of animal cells. The simplest of these are the polyoma virus and SV40 (Supplement 4-B). Following the integration of viral DNA into the host cell chromosome, some viral genes continue to be transcribed. Others remain inactive, much like phage λ. In rare cases, the incorporation of viral DNA into the host genome leads to cellular transformation into a tumor-like state. It remains unknown whether this is caused by specific viral gene products, alterations in the phenotypic expression of host genes, or Mutations (such as those occurring when phage λ integrates into the E. coli chromosome). What is clear, however, is that the Structure/108.html">Surface Properties of transformed cells are altered As a result. This, in turn, leads to a reduction in contact inhibition (Chapter 1, Section D, 3, c), ultimately resulting in the extensive proliferation of the transformed cells. Thus, a fundamental hallmark of tumors may stem from the integration of viral DNA into the genome of a normal cell [234, 235].