Rudolf Rott – författare

The fact that none of the known DNA polymerases is able to initiate DNA chains but only to elongate from a free 3'' -OH group raises the problem of how replication is initiated, both at the replication origin and on Okazaki frag­ ments. It was first shown by A. KORNBERG et al. that a general mechanism to initiate replication is through the formation of an RNA primer catalyzed by RNA polymerases or by a new class of enzymes, the primases (KORNBERG 1980). This mechanism, which can be used in the case of circular DNA molecules or linear DNAs that circularize or form concatemers, cannot be used at the ends of linear DNAs since the RNA primer is removed from the DNA chain, and there is no way of filling the gap resulting at the 5'' -ends of the newly synthesized DNA chain. In some cases linear DNA molecules contain a palin­ dromic nucleotide sequence at the 3'' -end that allows the formation of a hairpin structure which provides the needed free 3''-OH group for elongation. This mechanism, first proposed by CAVALIER-SMITH (1974) for eukaryotic DNA repli­ cation, was shown to take place in several systems (KORNBERG 1980, 1982). Another mechanism to initiate replication consists in the specific nicking of one of the strands of a circular double-stranded DNA, producing a 3''-OH group available for elongation (KORNBERG 1980).

The fact that none of the known DNA polymerases is able to initiate DNA chains but only to elongate from a free 3' -OH group raises the problem of how replication is initiated, both at the replication origin and on Okazaki frag­ ments. It was first shown by A. KORNBERG et al. that a general mechanism to initiate replication is through the formation of an RNA primer catalyzed by RNA polymerases or by a new class of enzymes, the primases (KORNBERG 1980). This mechanism, which can be used in the case of circular DNA molecules or linear DNAs that circularize or form concatemers, cannot be used at the ends of linear DNAs since the RNA primer is removed from the DNA chain, and there is no way of filling the gap resulting at the 5' -ends of the newly synthesized DNA chain. In some cases linear DNA molecules contain a palin­ dromic nucleotide sequence at the 3' -end that allows the formation of a hairpin structure which provides the needed free 3'-OH group for elongation. This mechanism, first proposed by CAVALIER-SMITH (1974) for eukaryotic DNA repli­ cation, was shown to take place in several systems (KORNBERG 1980, 1982). Another mechanism to initiate replication consists in the specific nicking of one of the strands of a circular double-stranded DNA, producing a 3'-OH group available for elongation (KORNBERG 1980).

Elucidation of the mechanisms of pathogenesis underlying the diseases caused by viruses and bacteria has fascinated scientists for many years in two ways. Firstly, these pathogenic agents represent relatively sim­ ple biological systems for the study of basic biological processes such as replication, gene regulation, genetic variability and host-pathogen interactions. Secondly, process in this field is valuable in a practi­ cal sence, since it can help in the control of these diseases. The avail­ ability of new genetic and immunological techniques, especially recom­ binant DNA methods and monoclonal antibody technology, has provided powerful tools for unravelling the genetic, biochemical and immunologi­ cal basis of viral and microbial pathogenesis. Molecular cloning has allowed the isolation of single genes or groups of genes related to phenotypes which appear to be immunologically important for pathogene­ sis. The specific elimination of such genes from the complex genomes of the pathogens can now be achieved with similar genetic techniques. These genetic studies have provided additional information on the role played by specific phenotypic traits in pathogenesis, especially when combined with relevant animal model systems. Furthermore, the struc­ tural analysis of important virulence factors and surface antigens may allow the prediction of antigenic domains suitable for the development of new vaccines. The 38th Mosbacher Colloquium focuses on the molecular basis of viral and microbial pathogenesis. The virology part begins with the well­ studied plant viroids. The unusual structure of their genome, as well as knowledge about their replication and pathogenicity, are presented.